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Yu, Bo, Nian Liu, Siqi Tang, Tian Qin, and Junli Huang. "Roles of Glutamate Receptor-Like Channels (GLRs) in Plant Growth and Response to Environmental Stimuli." Plants 11, no. 24 (December 9, 2022): 3450. http://dx.doi.org/10.3390/plants11243450.
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Plant glutamate receptor-like channels (GLRs) are the homologues of ionotropic glutamate receptors (iGluRs) that mediate neurotransmission in mammals, and they play important roles in various plant-specific physiological processes, such as pollen tube growth, sexual reproduction, root meristem proliferation, internode cell elongation, stomata aperture regulation, and innate immune and wound responses. Notably, these biological functions of GLRs have been mostly linked to the Ca2+-permeable channel activity as GLRs can directly channel the transmembrane flux of Ca2+, which acts as a key second messenger in plant cell responses to both endogenous and exogenous stimuli. Thus, it was hypothesized that GLRs are mainly involved in Ca2+ signaling processes in plant cells. Recently, great progress has been made in GLRs for their roles in long-distance signal transduction pathways mediated by electrical activity and Ca2+ signaling. Here, we review the recent progress on plant GLRs, and special attention is paid to recent insights into the roles of GLRs in response to environmental stimuli via Ca2+ signaling, electrical activity, ROS, as well as hormone signaling networks. Understanding the roles of GLRs in integrating internal and external signaling for plant developmental adaptations to a changing environment will definitely help to enhance abiotic stress tolerance.
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Grenzi, Matteo, Maria Cristina Bonza, and Alex Costa. "Signaling by plant glutamate receptor-like channels: What else!" Current Opinion in Plant Biology 68 (August 2022): 102253. http://dx.doi.org/10.1016/j.pbi.2022.102253.
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Meyerhoff, Oliver, Katharina Müller, M. Rob G. Roelfsema, Andreas Latz, Benoit Lacombe, Rainer Hedrich, Petra Dietrich, and Dirk Becker. "AtGLR3.4, a glutamate receptor channel-like gene is sensitive to touch and cold." Planta 222, no. 3 (April 28, 2005): 418–27. http://dx.doi.org/10.1007/s00425-005-1551-3.
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Toyota, Masatsugu, Dirk Spencer, Satoe Sawai-Toyota, Wang Jiaqi, Tong Zhang, Abraham J. Koo, Gregg A. Howe, and Simon Gilroy. "Glutamate triggers long-distance, calcium-based plant defense signaling." Science 361, no. 6407 (September 13, 2018): 1112–15. http://dx.doi.org/10.1126/science.aat7744.
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Animals require rapid, long-range molecular signaling networks to integrate sensing and response throughout their bodies. The amino acid glutamate acts as an excitatory neurotransmitter in the vertebrate central nervous system, facilitating long-range information exchange via activation of glutamate receptor channels. Similarly, plants sense local signals, such as herbivore attack, and transmit this information throughout the plant body to rapidly activate defense responses in undamaged parts. Here we show that glutamate is a wound signal in plants. Ion channels of the GLUTAMATE RECEPTOR–LIKE family act as sensors that convert this signal into an increase in intracellular calcium ion concentration that propagates to distant organs, where defense responses are then induced.
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Weiland, Matthias, Stefano Mancuso, and Frantisek Baluska. "Signalling via glutamate and GLRs in Arabidopsis thaliana." Functional Plant Biology 43, no. 1 (2016): 1. http://dx.doi.org/10.1071/fp15109.
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The genome of Arabidopsis thaliana (L. Heynh.) contains 20 coding sequences for homologues of animal ionotropic glutamate receptors. These glutamate receptor-like receptors act as sensors and mediators of a multitude of exogenous as well as endogenous signals and are found in all analysed plant species. Their molecular structure clearly indicates a function as integral membrane proteins with a ligand-gated ion channel activity. Altered gene expressions and the occurrence of mRNA splice variants confer a high flexibility on the gene as well as on the RNA level. An individual glutamate receptor of A. thaliana is able to bind two different ligands (most probable amino acids and their derivatives), whereas a functional receptor complex is likely to consist of four single proteins. These features enable an immense number of sensitivities against various local and temporal stimuli. This review encompasses the last 15 years of research concerning glutamate signalling and glutamate receptors in plants. It is aimed at summarising their major characteristics and involvements to obtain a broader and farer reaching perspective of these fundamental components of plant signal transduction.
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Li, Zhong-Guang, Xin-Yu Ye, and Xue-Mei Qiu. "Glutamate signaling enhances the heat tolerance of maize seedlings by plant glutamate receptor-like channels-mediated calcium signaling." Protoplasma 256, no. 4 (January 23, 2019): 1165–69. http://dx.doi.org/10.1007/s00709-019-01351-9.
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Shao, Qiaolin, Qifei Gao, Dhondup Lhamo, Hongsheng Zhang, and Sheng Luan. "Two glutamate- and pH-regulated Ca2+ channels are required for systemic wound signaling in Arabidopsis." Science Signaling 13, no. 640 (July 14, 2020): eaba1453. http://dx.doi.org/10.1126/scisignal.aba1453.
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Plants defend against herbivores and nematodes by rapidly sending signals from the wounded sites to the whole plant. We investigated how plants generate and transduce these rapidly moving, long-distance signals referred to as systemic wound signals. We developed a system for measuring systemic responses to root wounding in Arabidopsis thaliana. We found that root wounding or the application of glutamate to wounded roots was sufficient to trigger root-to-shoot Ca2+ waves and slow wave potentials (SWPs). Both of these systemic signals were inhibited by either disruption of both GLR3.3 and GLR3.6, which encode glutamate receptor–like proteins (GLRs), or constitutive activation of the P-type H+-ATPase AHA1. We further showed that GLR3.3 and GLR3.6 displayed Ca2+-permeable channel activities gated by both glutamate and extracellular pH. Together, these results support the hypothesis that wounding inhibits P-type H+-ATPase activity, leading to apoplastic alkalization. This, together with glutamate released from damaged phloem, activates GLRs, resulting in depolarization of membranes in the form of SWPs and the generation of cytosolic Ca2+ increases to propagate systemic wound signaling.
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Grenzi, Matteo, Maria Cristina Bonza, Andrea Alfieri, and Alex Costa. "Structural insights into long‐distance signal transduction pathways mediated by plant glutamate receptor‐like channels." New Phytologist 229, no. 3 (November 24, 2020): 1261–67. http://dx.doi.org/10.1111/nph.17034.
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Kwaaitaal, Mark, Rik Huisman, Jens Maintz, Anja Reinstädler, and Ralph Panstruga. "Ionotropic glutamate receptor (iGluR)-like channels mediate MAMP-induced calcium influx in Arabidopsis thaliana." Biochemical Journal 440, no. 3 (November 28, 2011): 355–73. http://dx.doi.org/10.1042/bj20111112.
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Binding of specific microbial epitopes [MAMPs (microbe-associated molecular patterns)] to PRRs (pattern recognition receptors) and subsequent receptor kinase activation are key steps in plant innate immunity. One of the earliest detectable events after MAMP perception is a rapid and transient rise in cytosolic Ca2+ levels. In plants, knowledge about the signalling events leading to Ca2+ influx and on the molecular identity of the channels involved is scarce. We used a transgenic Arabidopsis thaliana line stably expressing the luminescent aequorin Ca2+ biosensor to monitor pharmacological interference with Ca2+ signatures following treatment with the bacterial peptide MAMPs flg22 and elf18, and the fungal carbohydrate MAMP chitin. Using a comprehensive set of compounds known to impede Ca2+-transport processes in plants and animals we found strong evidence for a prominent role of amino acid-controlled Ca2+ fluxes, probably through iGluR (ionotropic glutamate receptor)-like channels. Interference with amino acid-mediated Ca2+ fluxes modulates MAMP-triggered MAPK (mitogen-activated protein kinase) activity and affects MAMP-induced accumulation of defence gene transcripts. We conclude that the initiation of innate immune responses upon flg22, elf18 and chitin recognition involves apoplastic Ca2+ influx via iGluR-like channels.
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Yang, Liu, Yumei Zhao, Xiaoyu Wu, Yang Zhang, Yehan Fu, Qiaohong Duan, Wei Ma, and Jiabao Huang. "Genome-Wide Identification and Expression Analysis of BraGLRs Reveal Their Potential Roles in Abiotic Stress Tolerance and Sexual Reproduction." Cells 11, no. 23 (November 22, 2022): 3729. http://dx.doi.org/10.3390/cells11233729.
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Glutamate receptors (GLRs) are involved in multiple functions during the plant life cycle through affecting the Ca2+ concentration. However, GLRs in Brassica species have not yet been reported. In this study, 16 glutamate receptor-like channels (GLR) belonged to two groups were identified in the Brassica rapa (B. rapa) genome by bioinformatic analysis. Most members contain domains of ANF_receptor, Peripla_BP_6, Lig_chan, SBP_bac_3, and Lig_chan_Glu_bd that are closely related to glutamate receptor channels. This gene family contains many elements associated with drought stress, low temperature stress, methyl jasmonate (MeJA), salicylic acid (SA), and other stress resistance. Gene expression profiles showed that BraGLR genes were expressed in roots, stems, leaves, flowers, and siliques. BraGLR5 expression was elevated after drought stress in drought-sensitive plants. BraGLR1, BraGLR8, and BraGLR11 expression were significantly upregulated after salt stress. BraGLR3 expression is higher in the female sterile-line mutants than in the wild type. The expression levels of BraGLR6, BraGLR9, BraGLR12, and BraGLR13 were significantly higher in the male sterile-line mutants than in the wild type. The expression of most BraGLRs increased after self-pollination, with BraGLR9 exhibiting the greatest increase. These results suggest that BraGLRs play an important role in abiotic stress tolerance and sexual reproduction.
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Yu, Bo, Ying Sun, Xinkai Jin, Zizhao Xie, Xingxing Li, and Junli Huang. "Rice glutamate receptor-like channel OsGLR3.4 modulates the root tropism growth towards amino acids via plasma membrane depolarization and ROS generation." Environmental and Experimental Botany 205 (January 2023): 105146. http://dx.doi.org/10.1016/j.envexpbot.2022.105146.
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Pozdnyakov, Ilya, Olga Matantseva, and Sergei Skarlato. "Consensus channelome of dinoflagellates revealed by transcriptomic analysis sheds light on their physiology." Algae 36, no. 4 (December 15, 2021): 315–26. http://dx.doi.org/10.4490/algae.2021.36.12.2.
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Ion channels are membrane protein complexes mediating passive ion flux across the cell membranes. Every organism has a certain set of ion channels that define its physiology. Dinoflagellates are ecologically important microorganisms characterized by effective physiological adaptability, which backs up their massive proliferations that often result in harmful blooms (red tides). In this study, we used a bioinformatics approach to identify homologs of known ion channels that belong to 36 ion channel families. We demonstrated that the versatility of the dinoflagellate physiology is underpinned by a high diversity of ion channels including homologs of animal and plant proteins, as well as channels unique to protists. The analysis of 27 transcriptomes allowed reconstructing a consensus ion channel repertoire (channelome) of dinoflagellates including the members of 31 ion channel families: inwardly-rectifying potassium channels, two-pore domain potassium channels, voltage-gated potassium channels (Kv), tandem Kv, cyclic nucleotide-binding domain-containing channels (CNBD), tandem CNBD, eukaryotic ionotropic glutamate receptors, large-conductance calcium-activated potassium channels, intermediate/small-conductance calcium-activated potassium channels, eukaryotic single-domain voltage-gated cation channels, transient receptor potential channels, two-pore domain calcium channels, four-domain voltage-gated cation channels, cation and anion Cys-loop receptors, small-conductivity mechanosensitive channels, large-conductivity mechanosensitive channels, voltage-gated proton channels, inositole-1,4,5- trisphosphate receptors, slow anion channels, aluminum-activated malate transporters and quick anion channels, mitochondrial calcium uniporters, voltage-dependent anion channels, vesicular chloride channels, ionotropic purinergic receptors, animal volage-insensitive cation channels, channelrhodopsins, bestrophins, voltage-gated chloride channels H+/Cl- exchangers, plant calcium-permeable mechanosensitive channels, and trimeric intracellular cation channels. Overall, dinoflagellates represent cells able to respond to physical and chemical stimuli utilizing a wide range of Gprotein coupled receptors- and Ca2+-dependent signaling pathways. The applied approach not only shed light on the ion channel set in dinoflagellates, but also provided the information on possible molecular mechanisms underlying vital cellular processes dependent on the ion transport.
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Philippe, Florian, Isabelle Verdu, Marie-Christine Morère-Le Paven, Anis M. Limami, and Elisabeth Planchet. "Involvement of Medicago truncatula glutamate receptor-like channels in nitric oxide production under short-term water deficit stress." Journal of Plant Physiology 236 (May 2019): 1–6. http://dx.doi.org/10.1016/j.jplph.2019.02.010.
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Demidchik, Vadim, and Sergey Shabala. "Mechanisms of cytosolic calcium elevation in plants: the role of ion channels, calcium extrusion systems and NADPH oxidase-mediated 'ROS-Ca2+ Hub'." Functional Plant Biology 45, no. 2 (2018): 9. http://dx.doi.org/10.1071/fp16420.
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Elevation in the cytosolic free calcium is crucial for plant growth, development and adaptation. Calcium influx into plant cells is mediated by Ca2+ depolarisation-activated, hyperpolarisation-activated and voltage-independent Ca2+-permeable channels (DACCs, HACCs and VICCs respectively). These channels are encoded by the following gene families: (1) cyclic nucleotide-gated channels (CNGCs), (2) ionotropic glutamate receptors (GLRs), (3) annexins, (4) ‘mechanosensitive channels of small (MscS) conductance’-like channels (MSLs), (5) ‘mid1-complementing activity’ channels (MCAs), Piezo channels, and hyperosmolality-induced [Ca2+]cyt. channel 1 (OSCA1). Also, a ‘tandem-pore channel1’ (TPC1) catalyses Ca2+ efflux from the vacuole in response to the plasma membrane-mediated Ca2+ elevation. Recent experimental data demonstrated that Arabidopsis thaliana (L.) Heynh. CNGCs 2, 5–10, 14, 16 and 18, GLRs 1.2, 3.3, 3.4, 3.6 and 3.7, TPC1, ANNEXIN1, MSL9 and MSL10,MCA1 and MCA2, OSCA1, and some their homologues counterparts in other species, are responsible for Ca2+ currents and/or cytosolic Ca2+ elevation. Extrusion of Ca2+ from the cytosol is mediated by Ca2+-ATPases and Ca2+/H+ exchangers which were recently examined at the level of high resolution crystal structure. Calcium-activated NADPH oxidases and reactive oxygen species (ROS)-activated Ca2+ conductances form a self-amplifying ‘ROS-Ca2+hub’, enhancing and transducing Ca2+ and redox signals. The ROS-Ca2+ hub contributes to physiological reactions controlled by ROS and Ca2+, demonstrating synergism and unity of Ca2+ and ROS signalling mechanisms.
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Yin, Hua, Dong Hyu Cho, Soo Joung Park, and Seong Kyu Han. "GABA-Mimetic Actions of Withania somnifera on Substantia Gelatinosa Neurons of the Trigeminal Subnucleus Caudalis in Mice." American Journal of Chinese Medicine 41, no. 05 (January 2013): 1043–51. http://dx.doi.org/10.1142/s0192415x13500705.
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The plant Withania somnifera (WS), also known as Ashwagandha, has been used widely in traditional medicine systems in India and Nepal (Ayurveda), and has been accepted to cure various ailments. In this study, the whole-cell patch clamp technique was performed to examine the mechanism of action of WS on the SG neurons of the Vc from mouse brainstem slices. In whole-cell patch clamp mode, methanol extract of Withania somnifera (mWS) induced short-lived and repeatable inward currents in all SG neurons tested (31.3±8.51 pA, n = 7) using a high chloride pipette solution. The mWS-induced inward currents were concentration dependent and maintained in the presence of tetrodotoxin (TTX), a voltage gated Na + channel blocker, CNQX, a non-NMDA glutamate receptor antagonist, AP5, an NMDA receptor antagonist and strychnine, a glycine receptor antagonist. The mWS induced currents were blocked by picrotoxin, a GABAA receptor antagonist. These results show that mWS has an inhibitory effects on SG neurons of the Vc through GABAA receptor-mediated activation of chloride ion channels, indicating that mWS contains compounds with sedative effects on the central nervous system. These results also suggest that mWS may be a potential target for modulating orofacial pain processing.
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Kwaaitaal, Mark, Jens Maintz, Meltem Cavdar, and Ralph Panstruga. "On the ligand binding profile and desensitization of plant ionotropic glutamate receptor (iGluR)-like channels functioning in MAMP-triggered Ca2+influx." Plant Signaling & Behavior 7, no. 11 (November 2012): 1373–77. http://dx.doi.org/10.4161/psb.21761.
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Ju, Chuanli, Dongdong Kong, Yuree Lee, Gege Ge, Yanan Song, Jiawen Liu, and June M. Kwak. "Methionine synthase 1 provides methionine for activation of the GLR3.5 Ca2+ channel and regulation of germination in Arabidopsis." Journal of Experimental Botany 71, no. 1 (September 30, 2019): 178–87. http://dx.doi.org/10.1093/jxb/erz431.
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Abstract Seed germination is a developmental process regulated by numerous internal and external cues. Our previous studies have shown that calcium influx mediated by the Arabidopsis glutamate receptor homolog 3.5 (AtGLR3.5) modulates the expression of the ABSCISIC ACID INSENSITIVE 4 (ABI4) transcription factor during germination and that L-methionine (L-Met) activates AtGLR3.1/3.5 Ca2+ channels in guard cells. However, it is not known whether L-Met participates in regulation of germination and what cellular mechanism is responsible for Met production during germination. Here, we describe Arabidopsis methionine synthase 1 (AtMS1), which acts in the final step of Met biosynthesis, synthesizes the Met required for the activation of AtGLR3.5 Ca2+ channels whose expression is up-regulated during germination, leading to the regulation of seed germination. We show that exogenous L-Met promotes germination in an AtGRL3.5-dependent manner. We also demonstrate that L-Met directly regulates the AtGLR3.5-mediated increase in cytosolic Ca2+ level in seedlings. We provide pharmacological and genetic evidence that Met synthesized via AtMS1 acts upstream of the AtGLR3.5-mediated Ca2+ signal and regulates the expression of ABI4, a major regulator in the abscisic acid response in seeds. Overall, our results link AtMS1, L-Met, the AtGLR3.5 Ca2+ channel, Ca2+ signals, and ABI4, and shed light on the physiological role and molecular mechanism of L-Met in germination.
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Lopes, Juliana Agostinho, Vinícius Peixoto Rodrigues, Marcelo Marucci Pereira Tangerina, Lucia Regina Machado da Rocha, Catarine Massucato Nishijima, Vania Vasti Alfieri Nunes, Luiz Fernando Rolim de Almeida, et al. "Machaerium hirtum (Vell.) Stellfeld Alleviates Acute Pain and Inflammation: Potential Mechanisms of Action." Biomolecules 10, no. 4 (April 11, 2020): 590. http://dx.doi.org/10.3390/biom10040590.
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Machaerium hirtum (Vell.) Stellfeld (Fabaceae) known in Brazil as “jacaranda de espinho” or “espinheira santa nativa” is a medicinal plant commonly used in folk medicine to treat ulcers, cough and diarrhea. This study aimed to investigate the anti-inflammatory and antinociceptive effects of hydroalcoholic extracts from M. hirtum twig (HEMh) using in vivo experimental models of nociception through the involvement of transient receptor potential channels, acid-sensing ion channel (ASIC), nitrergic, opioidergic, glutamatergic, and supraspinal pathways. Our results revealed an antinociceptive effect of HEMh mediated by the opioidergic, l-arginine-nitric oxide and glutamate systems, as well as by interactions with TRPA1/ASIC channels. The anti-inflammatory effect of HEMh evaluated with a xylene-induced ear edema and by the involvement of arachidonic acid and prostaglandin E2 (PGE2) showed involvement of the COX pathway, based on observed decreases in PGE2 levels. A phytochemical investigation of the HEMh led to the isolation of α-amyrin, β-amyrin, allantoin, apigenin-7-methoxy-6-C-β-d-glucopyranoside, and apigenin-6-C-β-d-glucopyranosyl-8-C-β-d-xylopyranoside. In conclusion, the acute oral administration of HEMh inhibits the nociceptive behavioral response in animals through the nitrergic, opioid, glutamatergic pathways, and by inhibition of the TRPA1 and ASIC channels, without causing locomotor dysfunction. In addition, its anti-inflammatory effect is associated with the COX pathway and decreased PGE2 levels.
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Kuronuma, Takanori, and Hitoshi Watanabe. "Search for Candidate Genes Causing the Excessive Ca Accumulation in Roots of Tipburn-Damaged Lisianthus (Eustoma grandiflorum) Cultivars." Agriculture 11, no. 3 (March 17, 2021): 254. http://dx.doi.org/10.3390/agriculture11030254.
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Occurrence of tipburn is a severe problem in the production of lisianthus cultivars. Previous studies have shown excessive Ca accumulation in the roots of tipburn-damaged cultivars, where the distribution of Ca to the tips of the top leaves is inhibited. However, few studies have investigated the association between Ca accumulation and gene expression in horticultural crops. To provide a list of candidate target genes that might be causing the excessive Ca accumulation in roots, we focused Ca2+ transporter and pectin methylesterase (PME) genes and RNA-seq of upper leaves and roots in tipburn-occurrence cultivar (“Voyage peach”: VP) and non-occurrence cultivar (“Umi honoka”: UH) was conducted. In both the upper leaves and roots of VP, genes encoding the glutamate receptors (GLRs), cation/Ca2+ exchangers 4 (CCX4), Na+/Ca2+ exchanger-like protein (NCL), and PMEs were upregulated, and a gene encoding the cyclic nucleotide-gated ion channel 9 (CNGC9) was downregulated. In contrast, genes encoding the vacuolar cation/proton exchanger 5 (CAX5), calcium-transporting ATPase 1 and 12 (ACA1 and ACA12) showed differential expression in each organ. Among them, only CAX5 was upregulated and ACA12 was downregulated in the roots of VP. Based on these results, we suggested that CAX5 and ACA12 are the candidate genes causing the excessive Ca accumulation in the roots of tipburn-occurrence lisianthus cultivars. Future studies should investigate the temporal changes in gene expression using quantitative PCR and conduct functional analysis of candidate genes in tipburn-damaged lisianthus cultivars.
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Green, Marriah N., Shanti Pal Gangwar, Erwan Michard, Alexander A. Simon, Maria Teresa Portes, Juan Barbosa-Caro, Michael M. Wudick, et al. "Structure of the Arabidopsis thaliana glutamate receptor-like channel GLR3.4." Molecular Cell 81, no. 15 (August 2021): 3216–26. http://dx.doi.org/10.1016/j.molcel.2021.05.025.
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Green, Marriah N., Shanti P. Gangwar, Erwan Michard, Alex A. Simon, Maria Teresa Portes, Juan Barbosa-Caro, Michael M. Wudick, et al. "Structure of the Arabidopsis thaliana glutamate receptor-like channel GLR3.4." Biophysical Journal 122, no. 3 (February 2023): 193a. http://dx.doi.org/10.1016/j.bpj.2022.11.1180.
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Jarvis, C. R., Z. G. Xiong, J. R. Plant, D. Churchill, W. Y. Lu, B. A. Macvicar, and J. F. Macdonald. "Neurotrophin Modulation of NMDA Receptors in Cultured Murine and Isolated Rat Neurons." Journal of Neurophysiology 78, no. 5 (November 1, 1997): 2363–71. http://dx.doi.org/10.1152/jn.1997.78.5.2363.
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Jarvis, C. R., Z.-G. Xiong, J. R. Plant, D. Churchill, W.-Y. Lu, B. A. MacVicar, and J. F. MacDonald. Neurotrophin modulation of NMDA receptors in cultured murine and isolated rat neurons. J. Neurophysiol. 78: 2363–2371, 1997. Patch-clamp and calcium imaging techniques were used to assess the acute effects of the neurotrophins, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and nerve growth factor (NGF), on the responses of cultured and acutely isolated hippocampal and cultured striatal neurons to the glutamate receptor agonist N-methyl-d-aspartic acid (NMDA). The effects of BDNF on NMDA-activated currents were examined in greater detail. Currents evoked by NMDA, and the accompanying changes in intracellular calcium, were enhanced by low concentrations of the neurotrophins (1–20 ng/ml). The potentiation by the neurotrophins was rapid in onset and offset (<1 s). The neurotrophins also reduced desensitization of these currents in most cells. The enhancement of NMDA-activated currents by BDNF was observed using both perforated and whole cell patch recording techniques and could be demonstrated in outside-out patches. Furthermore, its effects were not attenuated by pretreatment with the protein kinase inhibitors genistein or 1-(5-isoquinolynesulfony)2-methylpiperazine (H7). Therefore, the actions of BDNF do not appear to be mediated by phosphorylation. Similar enhancements were observed with NT-3 and NT-4 and with NGF despite the fact that hippocampal neurons lack TrkA receptors. All together this evidence suggests that the enhancement of NMDA-evoked currents is unlikely to be mediated through the activation of growth factor receptors. Modulation of NMDA responses by BDNF was dependent on the concentration of extracellular glycine. The most pronounced potentiation by BDNF was observed at low concentrations, whereas no potentiation was observed in saturating concentrations of glycine, suggesting that BDNF may have increased the affinity of the NMDA receptor for glycine. However, the competitive glycine-site antagonist 7-chloro-kynurenic acid blocked the enhancement by BDNF without shifting the dose-inhibition relationship for this antagonist, and Mg2+ consistently depressed the potentiation of NMDA-evoked currents by BDNF, indicating that BDNF does not alter glycine affinity. BDNF also reversibly increased the probability of opening of NMDA channels recorded from outside-out patches taken from cultured hippocampal neurons. Other unrelated peptides including dynorphin and somatostatin also caused a glycine-dependent enhancement of NMDA currents and depressed the currents in saturating concentrations of glycine. In contrast, a shortened analogue dynorphin (6-17), which lacks N-terminus glycine residues, and another peptide met-enkephalin were without effects on NMDA currents recorded in low concentrations of glycine. Our results suggest that neurotrophins and other peptides can serve as glycine-like ligands for the NMDA receptor.
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Chen, Juan, Donglai Ma, Jun Bao, Ying Zhang, and Guoxing Deng. "Roots of Astragalus propinquus Schischkin Regulate Transmembrane Iron Transport and Ferroptosis to Improve Cerebral Ischemia-Reperfusion Injury." Evidence-Based Complementary and Alternative Medicine 2022 (August 2, 2022): 1–16. http://dx.doi.org/10.1155/2022/7410865.
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Background. The dried roots of the Astragalus propinquus Schischkin (RAP) plant, as a traditional Chinese medicine, has been widely used to treat stroke, cerebral ischemia, qi deficiency, and hypertension. Buyang Huanwu decoction is traditionally used to treat stroke in China for more than 200 years and has a significant effect on cerebral ischemia, and RAP is monarch medicine of Buyang Huanwu decoction. Therefore, this study was designed to observe the regulatory effect of RAP on transmembrane iron transporters and ferroptosis-related factors in cerebral ischemia-reperfusion injury (CIRI) in rats. Methods. Middle cerebral artery occlusion (MCAO) was used to block blood flow in the blood supply area of the middle cerebral artery in seventy male SD rats to induce focal CIRI to establish a rat model of CIRI. RAP was administered to explore the regulatory effect of RAP on iron transmembrane transport under the condition of CIRI. The infarct size was measured using 2,3,5-triphenyl-tetrazolium chloride (TTC) staining, the pathological structure of brain tissue was observed by HE staining, and neuronal injury was evaluated by Nissl staining after treatment. Then, changes in the iron transporters ferritin (Fn), ferritin heavy chain (FHC), ferritin light chain (FLC), transferrin (Tf), transferrin receptor (TfR), divalent metal transporter 1 (DMT1), L-type calcium channel (LTCC), transient receptor potential canonical 6 (TRPC6), and ferroportin 1 (FPN1) were observed by immunohistochemistry staining (IHC) and Western blotting. The expression of key factors of ferroptosis, including the membrane sodium-dependent cystine/glutamate antiporter System Xc− (System Xc−) light chain subunit (XCT) and heavy chain subunit (SLC3A2), glutathione peroxidase 4 (GPX4), nuclear factor erythroid 2-related factor (NRF2), heme oxygenase-1 (HO-1), and iron-responsive element-binding protein 2 (IREB2) in the brain tissues of rats was assessed by Western blotting. RAP decreased the infarct size and neuronal injury after CIRI in rats. Similarly, RAP treatment regulated the expression of iron transporters. As such, RAP was able to reduce the expression of Fn, FHC, FLC, Tf, TfR, DMT1, and TRPC6 and increase the expression of FPN1 through a Tf/TfR-independent pathway after CIRI in rats. Conclusion. RAP stimulation inhibited ferroptosis by regulating the expression of the key ferroptosis factors XCT, SLC3A2, GPX4, NRF2, HO-1, and IREB2. In conclusion, RAP regulates transmembrane iron transport and ferroptosis to improve CIRI.
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Grant, George B., and Frank S. Werblin. "A glutamate-elicited chloride current with transporter-like properties in rod photoreceptors of the tiger salamander." Visual Neuroscience 13, no. 1 (January 1996): 135–44. http://dx.doi.org/10.1017/s0952523800007185.
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AbstractGlutamate, when puffed near the synaptic terminals, elicits a current in rod photoreceptors. The current is strongly dependent upon both the intracellular and extracellular chloride concentration: its reversal potential follows the predicted Nernst potential for a chloride permeable channel. The glutamate-elicited current also requires the presence of extracellular sodium. This glutamate-elicited current is pharmacologically like a glutamate transporter: it is elicited, in order of efficacy, by L-glutamate, L-aspartate, L-cysteate, D-aspartate, and D-glutamate, all shown to activate glutamate transport in other systems. Furthermore, it is reduced by the glutamate transport antagonists dihydrokainate (DHKA) and D, L-threo-3–hydroxyaspartate (THA). THA, when applied alone, elicits a current similar to that elicited by glutamate. The current cannot be activated by the glutamate receptor agonists kainate, quisqualate, NMDA and APB, nor can it be blocked by the glutamale receptor antagonists CNQX and APV. Thus, the current does not appear to be mediated by a conventional glutamate receptor. Taken together, the ionic dependence and pharmacology of this current suggest that it is generated by glutamate transporter coupled to a chloride channel.
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Naz, Ruphi, Andleeb Khan, Badrah S. Alghamdi, Ghulam Md Ashraf, Maimonah Alghanmi, Altaf Ahmad, Sheikh Shanawaz Bashir, and Qazi Mohd Rizwanul Haq. "An Insight into Animal Glutamate Receptors Homolog of Arabidopsis thaliana and Their Potential Applications—A Review." Plants 11, no. 19 (September 30, 2022): 2580. http://dx.doi.org/10.3390/plants11192580.
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Most excitatory impulses received by neurons are mediated by ionotropic glutamate receptors (iGluRs). These receptors are located at the apex and play an important role in memory, neuronal development, and synaptic plasticity. These receptors are ligand-dependent ion channels that allow a wide range of cations to pass through. Glutamate, a neurotransmitter, activates three central ionotropic receptors: N-methyl-D-aspartic acid (NMDA), -amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA), and kainic acid (KA). According to the available research, excessive glutamate release causes neuronal cell death and promotes neurodegenerative disorders. Arabidopsis thaliana contains 20 glutamate receptor genes (AtGluR) comparable to the human ionotropic glutamate (iGluRs) receptor. Many studies have proved that AtGL-rec genes are involved in a number of plant growth and physiological activities, such as in the germination of seeds, roots, abiotic and biotic stress, and cell signaling, which clarify the place of these genes in plant biology. In spite of these, the iGluRs, Arabidopsis glutamate receptors (AtGluR), is associated with the ligand binding activity, which confirms the evolutionary relationship between animal and plant glutamate receptors. Along with the above activities, the impact of mammalian agonists and antagonists on Arabidopsis suggests a correlation between plant and animal glutamate receptors. In addition, these glutamate receptors (plant/animal) are being utilized for the early detection of neurogenerative diseases using the fluorescence resonance energy transfer (FRET) approach. However, a number of scientific laboratories and institutes are consistently working on glutamate receptors with different aspects. Currently, we are also focusing on Arabidopsis glutamate receptors. The current review is focused on updating knowledge on AtGluR genes, their evolution, functions, and expression, and as well as in comparison with iGluRs. Furthermore, a high throughput approach based on FRET nanosensors developed for understanding neurotransmitter signaling in animals and plants via glutamate receptors has been discussed. The updated information will aid in the future comprehension of the complex molecular dynamics of glutamate receptors and the exploration of new facts in plant/animal biology.
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Picaud, S. A., H. P. Larsson, G. B. Grant, H. Lecar, and F. S. Werblin. "Glutamate-gated chloride channel with glutamate-transporter-like properties in cone photoreceptors of the tiger salamander." Journal of Neurophysiology 74, no. 4 (October 1, 1995): 1760–71. http://dx.doi.org/10.1152/jn.1995.74.4.1760.
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1. Using the patch-clamp technique, we investigated whether the glutamate-elicited current in mechanically isolated cone photoreceptors from the salamander retina is generated by a Cl- channel or a glutamate transporter. 2. The current reversed near the equilibrium potential for Cl-, was decreased by three Cl- channel blockers, 5-nitro-2-(3-phenyl-propylamino) benzoic acid, 4,4'-diisothiocyanostilbene-2,2'-disulfonate, and diphenylamine 2,2'-dicarboxylic acid, and was eliminated when gluconate was substituted for both internal and external Cl-, features consistent with the current being mediated by a Cl- channel. 3. The single-channel conductance of the Cl- channel was estimated by noise analysis of the glutamate-elicited current fluctuations to be 0.7 pS with an open time of 2 ms. 4. The magnitude of the current was dependent on both internal and external Na+ and K+, features consistent with the current being related to the activation of a glutamate transporter. Yet changes in their concentrations did not affect the reversal potential of the current. 5. Taken together with earlier reports on this current showing that it has a glutamate-transporter-like pharmacology, our results suggest that the glutamate-elicited current is carried by a Cl- channel but gated by a glutamate receptor whose pharmacology and ionic requirement resemble those previously described for glutamate transporters.
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Shi, Edward Y., Christine L. Yuan, Matthew T. Sipple, Jayasri Srinivasan, Christopher P. Ptak, Robert E. Oswald, and Linda M. Nowak. "Noncompetitive antagonists induce cooperative AMPA receptor channel gating." Journal of General Physiology 151, no. 2 (January 8, 2019): 156–73. http://dx.doi.org/10.1085/jgp.201812209.
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Glutamate is released from presynaptic nerve terminals in the central nervous system (CNS) and spreads excitation by binding to and activating postsynaptic iGluRs. Of the potential glutamate targets, tetrameric AMPA receptors mediate fast, transient CNS signaling. Each of the four AMPA subunits in the receptor channel complex is capable of binding glutamate at its ligand-binding domains and transmitting the energy of activation to the pore domain. Homotetrameric AMPA receptor channels open in a stepwise manner, consistent with independent activation of individual subunits, and they exhibit complex kinetic behavior that manifests as temporal shifts between four different conductance levels. Here, we investigate how two AMPA receptor-selective noncompetitive antagonists, GYKI-52466 and GYKI-53655, disrupt the intrinsic step-like gating patterns of maximally activated homotetrameric GluA3 receptors using single-channel recordings from cell-attached patches. Interactions of these 2,3-benzodiazepines with residues in the boundary between the extracellular linkers and transmembrane helical domains reorganize the gating behavior of channels. Low concentrations of modulators stabilize open and closed states to different degrees and coordinate the activation of subunits so that channels open directly from closed to higher conductance levels. Using kinetic and structural models, we provide insight into how the altered gating patterns might arise from molecular contacts within the extracellular linker-channel boundary. Our results suggest that this region may be a tunable locus for AMPA receptor channel gating.
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Degani-Katzav, Nurit, Revital Gortler, Lilach Gorodetzki, and Yoav Paas. "Subunit stoichiometry and arrangement in a heteromeric glutamate-gated chloride channel." Proceedings of the National Academy of Sciences 113, no. 5 (January 20, 2016): E644—E653. http://dx.doi.org/10.1073/pnas.1423753113.
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The invertebrate glutamate-gated chloride-selective receptors (GluClRs) are ion channels serving as targets for ivermectin (IVM), a broad-spectrum anthelmintic drug used to treat human parasitic diseases like river blindness and lymphatic filariasis. The native GluClR is a heteropentamer consisting of α and β subunit types, with yet unknown subunit stoichiometry and arrangement. Based on the recent crystal structure of a homomeric GluClαR, we introduced mutations at the intersubunit interfaces where Glu (the neurotransmitter) binds. By electrophysiological characterization of these mutants, we found heteromeric assemblies with two equivalent Glu-binding sites at β/α intersubunit interfaces, where the GluClβ and GluClα subunits, respectively, contribute the “principal” and “complementary” components of the putative Glu-binding pockets. We identified a mutation in the IVM-binding site (far away from the Glu-binding sites), which significantly increased the sensitivity of the heteromeric mutant receptor to both Glu and IVM, and improved the receptor subunits’ cooperativity. We further characterized this heteromeric GluClR mutant as a receptor having a third Glu-binding site at an α/α intersubunit interface. Altogether, our data unveil heteromeric GluClR assemblies having three α and two β subunits arranged in a counterclockwise β-α-β-α-α fashion, as viewed from the extracellular side, with either two or three Glu-binding site interfaces.
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Vincill, Eric D., Arielle E. Clarin, Jennifer N. Molenda, and Edgar P. Spalding. "Interacting Glutamate Receptor-Like Proteins in Phloem Regulate Lateral Root Initiation in Arabidopsis." Plant Cell 25, no. 4 (April 2013): 1304–13. http://dx.doi.org/10.1105/tpc.113.110668.
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Karim, AR, and S. Jacob. "Experience with newer central nervous system autoantibodies." Annals of Clinical Biochemistry: International Journal of Laboratory Medicine 55, no. 1 (October 5, 2017): 7–17. http://dx.doi.org/10.1177/0004563217724818.
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In the last decade, a large number of neuronal cell-surface antibodies have been described which are responsible for a range of neuroimmunological central nervous system disorders. Unlike the paraneoplastic antibodies which target intracellular antigens, these antibodies appear to be pathogenic and hence identification and prompt treatment can make a substantial impact on clinical outcomes of these patients. We review the common antibodies against the ionotropic glutamate receptors (NMDAR, AMPAR), metabotropic glutamate receptors (mGluR1 and mGluR5), voltage-gated potassium channel-complex proteins (LGI1, CASPR2), and other antibodies targeted against glycine receptor, glutamic acid decarboxylase, gamma-amino butyric acid B, dopamine-2-receptor and dipeptidyl-peptidase-like protein 6.
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Holmes, K. H., N. B. Keele, V. L. Arvanov, and P. Shinnick-Gallagher. "Metabotropic glutamate receptor agonist-induced hyperpolarizations in rat basolateral amygdala neurons: receptor characterization and ion channels." Journal of Neurophysiology 76, no. 5 (November 1, 1996): 3059–69. http://dx.doi.org/10.1152/jn.1996.76.5.3059.
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1. Metabotropic glutamate receptor (mGluR)-agonist-induced hyperpolarizations and corresponding outward currents were analyzed in basolateral amygdala (BLA) neurons in rat brain slice preparations with current-clamp and single-electrode voltage-clamp recording to characterize the mGluR subtype(s) and the ion channel(s) mediating this response. 2. The mGluR agonist (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) induced a membrane hyperpolarization or outward current in BLA neurons in a concentration-dependent manner (median effective concentration = 34 microM; range = 10-200 microM); the 1S,3R-ACPD hyperpolarizations are recorded in 89% of neurons that accommodate or cease firing in response to a 400-ms depolarizing current injection (0.5 nA). 3. mGluR agonists elicited hyperpolarizations or outward currents in a concentration-dependent manner in the following rank order of potency: (2S,3S,4S)-alpha-(carboxycyclopropyl)glycine (L-CCG-I) > 1S,3R-ACPD > (s)-4-carboxyphenylglycine = (RS)-4-carboxy-3-hydroxyphenylglycine (4C3HPG) > L-aminophosphonobutyric acid > (1S,3S)-1-amino-cyclopentane-1,3-dicarboxylic acid. In contrast, the mGluR agonists quisqualate and ibotenate induced only depolarizations in the presence of D-2-amino-5-phosphonovalerate and 6-cyano-7-nitroquinoxaline-2,3-dione in BLA neurons. 4. The 1S,3R-ACPD-induced outward current is mediated through a large-conductance calcium-dependent potassium (BK) conductance. The BK channel blockers iberiotoxin and charybdotoxin blocked the response, as did the potassium channel blockers tetraethylammonium and 4-aminopyridine; the small-conductance calcium-activated potassium channel blocker apamin did not affect the response. 5. The mGluR-agonist-induced hyperpolarization is blocked in amygdala slices from animals pretreated with pertussis toxin (PTX). 1S,3R-ACPD hyperpolarizations were recorded in neurons contralateral but not ipsilateral to the site of PTX injection. 6. The antagonist (+/-)-alpha-methyl-4-carboxyphenylglycine (MCPG, 500 microM) reduced significantly the 1S,3R-ACPD-induced hyperpolarization. 7. In conclusion, the relative potency of L-CCG-I and 4C3HPG in evoking only hyperpolarizations (outward currents) in accommodating neurons, and the observation that MCPG (500 microM) reduces the hyperpolarization, suggest that a group-II-like mGluR underlies the hyperpolarizing response. The mGluR-induced response is sensitive to iberiotoxin and to pretreatment with PTX, suggesting activation of BK channels through a group II mGluR linked to a PTX-sensitive G protein in BLA neurons.
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Feng, Shuxian, Caizhe Pan, Shuting Ding, Qiaomei Ma, Chaoyi Hu, Ping Wang, and Kai Shi. "The Glutamate Receptor Plays a Role in Defense against Botrytis cinerea through Electrical Signaling in Tomato." Applied Sciences 11, no. 23 (November 25, 2021): 11217. http://dx.doi.org/10.3390/app112311217.
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Plant glutamate-like receptor genes (GLRs) are homologous to mammalian ionotropic glutamate receptors genes (iGluRs). Although GLRs have been implicated in plant defenses to biotic stress, the relationship between GLR-mediated plant immunity against fungal pathogens and electrical signals remains poorly understood. Here, we found that pretreatment with a GLR inhibitor, 6,7-dinitriquinoxaline-2,3-dione (DNQX), increased the susceptibility of tomato plants to the necrotrophic fungal pathogen Botrytis cinerea. Assessment of the glr3.3, glr3.5 and glr3.3/glr3.5 double-mutants upon B. cinerea infection showed that tomato GLR3.3 and GLR3.5 are essential for plant immunity against B. cinerea, wherein GLR3.3 plays the main role. Analysis of the membrane potential changes induced by glutamate (Glu) or glycine (Gly) revealed that amplitude was significantly reduced by knocking out GLR3.3 in tomato. While treatment with Glu or Gly significantly increased immunity against B. cinerea in wild-type plants, this effect was significantly attenuated in glr3.3 mutants. Thus, our data demonstrate that GLR3.3- and GLR3.5-mediated plant immunity against B. cinerea is associated with electrical signals in tomato plants.
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Osorio, Héctor, Patricio Tapia-Reyes, Daniela Espinoza, Daniel Laporte, Alberto González, Eduardo Castro-Nallar, and Alejandra Moenne. "The Genome of the Marine Alga Ulva compressa (Chlorophyta) Reveals Protein-Coding Genes with Similarity to Plants and Green Microalgae, but Also to Animal, Bacterial, and Fungal Genes." International Journal of Molecular Sciences 23, no. 13 (June 30, 2022): 7279. http://dx.doi.org/10.3390/ijms23137279.
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The genome of the marine alga Ulva compressa was assembled using long and short reads. The genome assembly was 80.8 Mb in size and encoded 19,207 protein-coding genes. Several genes encoding antioxidant enzymes and a few genes encoding enzymes that synthesize ascorbate and glutathione were identified, showing similarity to plant and bacterial enzymes. Additionally, several genes encoding signal transduction protein kinases, such as MAPKs, CDPKS, CBLPKs, and CaMKs, were also detected, showing similarity to plants, green microalgae, and bacterial proteins. Regulatory transcription factors, such as ethylene- and ABA-responsive factors, MYB, WRKY, and HSTF, were also present and showed similarity to plant and green microalgae transcription factors. Genes encoding enzymes that synthesize ACC and ABA-aldehyde were also identified, but oxidases that synthesize ethylene and ABA, as well as enzymes that synthesize other plant hormones, were absent. Interestingly, genes involved in plant cell wall synthesis and proteins related to animal extracellular matrix were also detected. Genes encoding cyclins and CDKs were also found, and CDKs showed similarity to animal and fungal CDKs. Few genes encoding voltage-dependent calcium channels and ionotropic glutamate receptors were identified as showing similarity to animal channels. Genes encoding Transient Receptor Potential (TRP) channels were not identified, even though TRPs have been experimentally detected, indicating that the genome is not yet complete. Thus, protein-coding genes present in the genome of U. compressa showed similarity to plant and green microalgae, but also to animal, bacterial, and fungal genes.
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Shinno, Hideto, Masahiko Mikuni, Kazuko Saitoh, Urara Tomita, Shigeto Yamawaki, and Kiyohisa Takahashi. "Metabotropic Glutamate Receptor in C6BU-1 Glioma Cell Has NMDA Receptor-Ion Channel Complex-Like Properties and Interacts with Serotonin2 Receptor-Stimulated Signal Transduction." Journal of Neurochemistry 63, no. 4 (November 23, 2002): 1346–53. http://dx.doi.org/10.1046/j.1471-4159.1994.63041346.x.
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Dave, Kathleen A., Jean-Claude Platel, Frank Huang, David Tian, Severine Stamboulian-Platel, and Angélique Bordey. "Prostaglandin E2 induces glutamate release from subventricular zone astrocytes." Neuron Glia Biology 6, no. 3 (August 2010): 201–7. http://dx.doi.org/10.1017/s1740925x10000244.
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It was recently reported that in one of the adult neurogenetic zones, the subventricular zone (SVZ), astrocyte-like cells release glutamate upon intracellular Ca2+ increases. However, the signals that control Ca2+ activity and glutamate release from SVZ astrocytes are not known. Here, we examined whether prostaglandin E2 (PGE2), which induces glutamate release from mature astrocytes, is such a signal. Using the gramicidin-perforated patch-clamp technique, we show that the activity of N-Methyl-D-Aspartate receptor (NMDAR) channel in neuroblasts is a high fidelity sensor of ambient glutamate levels. Using such sensors, we found that application of PGE2 led to increased ambient glutamate levels in the SVZ. In parallel experiments, PGE2 induced an increase in intracellular Ca2+ levels in SVZ cells, in particular astrocyte-like cells, as shown using Ca2+ imaging. Finally, a PGE2 enzyme immunoassay showed that the choroid plexus of the lateral ventricle and to a lesser extent the SVZ (ten-fold less) released PGE2. These findings suggest that PGE2 is a physiological signal for inducing glutamate release from SVZ astrocytes that is important for controlling neuroblast survival and proliferation. This signal may be accentuated following ischemia or injury-induced PGE2 release and may contribute to the injury-associated increased neurogenesis.
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Twomey, Edward C., Maria V. Yelshanskaya, and Alexander I. Sobolevsky. "Structural and functional insights into transmembrane AMPA receptor regulatory protein complexes." Journal of General Physiology 151, no. 12 (October 15, 2019): 1347–56. http://dx.doi.org/10.1085/jgp.201812264.
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Fast excitatory neurotransmission is mediated by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype of ionotropic glutamate receptor (AMPAR). AMPARs initiate depolarization of the postsynaptic neuron by allowing cations to enter through their ion channel pores in response to binding of the neurotransmitter glutamate. AMPAR function is dramatically affected by auxiliary subunits, which are regulatory proteins that form various complexes with AMPARs throughout the brain. The most well-studied auxiliary subunits are the transmembrane AMPAR regulatory proteins (TARPs), which alter the assembly, trafficking, localization, kinetics, and pharmacology of AMPARs. Recent structural and functional studies of TARPs and the TARP-fold germ cell-specific gene 1-like (GSG1L) subunit have provided important glimpses into how auxiliary subunits regulate the function of synaptic complexes. In this review, we put these recent structures in the context of new functional findings in order to gain insight into the determinants of AMPAR regulation by TARPs. We thus reveal why TARPs display a broad range of effects despite their conserved modular architecture.
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Boldt, Wolfgang, Manuela Klapperstück, Cora Büttner, Sven Sadtler, Günther Schmalzing, and Fritz Markwardt. "Glu496Ala polymorphism of human P2X7receptor does not affect its electrophysiological phenotype." American Journal of Physiology-Cell Physiology 284, no. 3 (March 1, 2003): C749—C756. http://dx.doi.org/10.1152/ajpcell.00042.2002.
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A glutamate to alanine exchange at amino acid position 496 of the human P2X7 receptor was recently shown to be associated with a loss of function in human B lymphocytes in terms of ATP-induced ethidium+ uptake, Ba2+ influx, and induction of apoptosis (Gu BJ, Zhang WY, Worthington RA, Sluyter R, Dao-Ung P, Petrou S, Barden JA, and Wiley JS. J Biol Chem 276: 11135–11142, 2001). Here we analyzed the effect of the Glu496 to Ala exchange on the channel properties of the human P2X7 receptor expressed in Xenopus oocytes with the two-microelectrode voltage-clamp technique. The amplitudes of ATP-induced whole cell currents characteristic of functional expression, kinetic properties including ATP concentration dependence, and permeation behavior were not altered by this amino acid exchange. Also in HEK293 cells, the Ala496 mutant mediated typical P2X7 receptor-dependent currents like the parent Glu496 hP2X7 receptor. Because the function of the P2X7 receptor as an ATP-gated channel for small cations including Ba2+ remained unaffected by this mutation, we conclude that Glu496 plays a critical role in pore formation but does not determine the ion channel properties of the human P2X7 receptor.
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Ene, F. Aura, Abigail Kalmbach, and Karl Kandler. "Metabotropic Glutamate Receptors in the Lateral Superior Olive Activate TRP-Like Channels: Age- and Experience-Dependent Regulation." Journal of Neurophysiology 97, no. 5 (May 2007): 3365–75. http://dx.doi.org/10.1152/jn.00686.2006.
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The lateral superior olive (LSO) is the primary auditory nucleus for processing of interaural sound level differences, which is one of the major cues for sound localization. During development, survival and maturation of LSO neurons critically depend on synaptic activity and intracellular calcium signaling. Before hearing onset, glutamatergic synaptic inputs from the cochlear nucleus (CN) to the LSO activate group I metabotropic glutamate receptors (mGluRs), which leads to calcium release from intracellular stores and large calcium influx from the extracellular milieu. Here, we investigated the nature of the mGluR-activated membrane channel that mediates the influx of extracellular calcium. Using Fura-2 calcium imaging in brain stem slices of neonatal and juvenile mice, we found that this calcium channel is blocked by Ni2+, La3+, and 2-aminoethoxydiphenylborane (2-APB), known antagonists of transient receptor potential (TRP) channels. During postnatal development, the contribution of extracellular calcium influx to mGluR-mediated Ca2+ responses gradually decreased and was almost abolished by the end of the third postnatal week. Over this period, the contribution of Ca2+ release from internal stores remained unchanged. The developmental decrease of TRP-like channel-mediated calcium influx was significantly less in congenitally deaf waltzer mice, suggesting that early auditory experience is necessary for the normal age-dependent downregulation of functional TRP channels.
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Poulsen, Mette H., Anahita Poshtiban, Viktoria Klippenstein, Valentina Ghisi, and Andrew J. R. Plested. "Gating modules of the AMPA receptor pore domain revealed by unnatural amino acid mutagenesis." Proceedings of the National Academy of Sciences 116, no. 27 (June 18, 2019): 13358–67. http://dx.doi.org/10.1073/pnas.1818845116.
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Ionotropic glutamate receptors (iGluRs) are responsible for fast synaptic transmission throughout the vertebrate nervous system. Conformational changes of the transmembrane domain (TMD) underlying ion channel activation and desensitization remain poorly understood. Here, we explored the dynamics of the TMD of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type iGluRs using genetically encoded unnatural amino acid (UAA) photocross-linkers, p-benzoyl-l-phenylalanine (BzF) and p-azido-l-phenylalanine (AzF). We introduced these UAAs at sites throughout the TMD of the GluA2 receptor and characterized the mutants in patch-clamp recordings, exposing them to glutamate and ultraviolet (UV) light. This approach revealed a range of optical effects on the activity of mutant receptors. We found evidence for an interaction between the Pre-M1 and the M4 TMD helix during desensitization. Photoactivation at F579AzF, a residue behind the selectivity filter in the M2 segment, had extraordinarily broad effects on gating and desensitization. This observation suggests coupling to other parts of the receptor and like in other tetrameric ion channels, selectivity filter gating.
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Palazzo, E., S. Boccella, I. Marabese, G. Pierretti, F. Guida, and S. Maione. "The Cold Case of Metabotropic Glutamate Receptor 6: Unjust Detention in the Retina?" Current Neuropharmacology 18, no. 2 (January 23, 2020): 120–25. http://dx.doi.org/10.2174/1570159x17666191001141849.
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It is a common opinion that metabotropic glutamate receptor subtype 6 (mGluR6) is expressed exclusively in the retina, and in particular in the dendrites of ON-bipolar cells. Glutamate released in darkness from photoreceptors activates mGluR6, which is negatively associated with a membrane non-selective cation channel, the transient receptor potential melanoma-related 1, TRPM1, resulting in cell hyperpolarization. The evidence that mGluR6 is expressed not only in the retina but also in other tissues and cell populations has accumulated over time. The expression of mGluR6 has been identified in microglia, bone marrow stromal and prostate cancer cells, B lymphocytes, melanocytes and keratinocytes and non-neural tissues such as testis, kidney, cornea, conjunctiva, and eyelid. The receptor also appears to be expressed in brain areas, such as the hypothalamus, cortex, hippocampus, nucleus of tractus solitarius, superior colliculus, axons of the corpus callosum and accessory olfactory bulb. The pharmacological activation of mGluR6 in the hippocampus produced an anxiolytic-like effect and in the periaqueductal gray analgesic potential. This review aims to collect all the evidence on the expression and functioning of mGluR6 outside the retina that has been accumulated over the years for a broader view of the potential of the receptor whose retinal confinement appears understimated.
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Goto, Yukihisa, Noriko Maki, Yasunori Ichihashi, Daisuke Kitazawa, Daisuke Igarashi, Yasuhiro Kadota, and Ken Shirasu. "Exogenous Treatment with Glutamate Induces Immune Responses in Arabidopsis." Molecular Plant-Microbe Interactions® 33, no. 3 (March 2020): 474–87. http://dx.doi.org/10.1094/mpmi-09-19-0262-r.
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Plant resistance inducers (PRIs) are compounds that protect plants from diseases by activating immunity responses. Exogenous treatment with glutamate (Glu), an important amino acid for all living organisms, induces resistance against fungal pathogens in rice and tomato. To understand the molecular mechanisms of Glu-induced immunity, we used the Arabidopsis model system. We found that exogenous treatment with Glu induces resistance against pathogens in Arabidopsis. Consistent with this, transcriptome analyses of Arabidopsis seedlings showed that Glu significantly induces the expression of wound-, defense-, and stress-related genes. Interestingly, Glu activates the expression of genes induced by pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns at much later time points than the flg22 peptide, which is a bacterial-derived PAMP. The Glu receptor-like (GLR) proteins GLR3.3 and GLR3.6 are involved in the early expression of Glu-inducible genes; however, the sustained expression of these genes does not require the GLR proteins. Glu-inducible gene expression is also not affected by mutations in genes that encode PAMP receptors (EFR, FLS2, and CERK1), regulators of pattern-triggered immunity (BAK1, BKK1, BIK1, and PBL1), or a salicylic acid biosynthesis enzyme (SID2). The treatment of roots with Glu activates the expression of PAMP-, salicylic acid-, and jasmonic acid-inducible genes in leaves. Moreover, the treatment of roots with Glu primes chitin-induced responses in leaves, possibly through transcriptional activation of LYSIN-MOTIF RECEPTOR-LIKE KINASE 5 (LYK5), which encodes a chitin receptor. Because Glu treatment does not cause discernible growth retardation, Glu can be used as an effective PRI.
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Dannhardt, G., and B. K. Kohl. "The Glycine Site on the NMDA Receptor: Structure-Activity Relationships and Possible Therapeutic Applications." Current Medicinal Chemistry 5, no. 4 (August 1998): 253–63. http://dx.doi.org/10.2174/0929867305666220314214937.
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L-glutamate is the most important fast excitatory neurotransmitter in the mammalian central nervous system. Glutamate receptors are classified into two main categories: ionotropic and metabotropic. The N-methyi-D-aspartate (NMDA) receptor, which is associated with an ion channel, seems to play an important role in glutamate excitotoxicity, a process thought to be involved in a number of neurodegenerative disorders such as focal cerebral ischaemia (stroke), Parkinsonfs, Huntingtonfs, Alzheimerfs disease, schizophrenia and epilepsy. The unique glycine site on the NMDA receptor, discovered by Johnson and Ascher in 1987, represents an interesting target for the development of neuroprotective compounds. Glycine antagonists may offer advantages over other NMDA antagonists in terms of their side-effect profile, especially in the long-term treatment of chronical neurodegenerative disorders but also _in the treatment of serious medical emergencies with a significant morbidity and mortality like status epilepticus or stroke. So far it is not clear whether NMDA receptor antagonists including glycine antagonists would be suitable for chronic administration because of their effects on cognition, learning and motor function. High-affinity, in vivo potent, glycine antagonists of great structural diversity (i. e. pyrido[2,3-b]pyrazine-N-oxides, indole-2 carboxylates, 4-substituted-3-phenylquinoline-2(1H) ones and alkyl-substituted 1,4-dihydro-quinoxaline-2,3-diones) are now available and their suitability for long-term treatment of chronical neurodegenerative disorders has to be investigated in clinical trials.
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Zhang, Jing, Tianzhen Cui, Yachun Su, Shoujian Zang, Zhennan Zhao, Chang Zhang, Wenhui Zou, et al. "Genome-Wide Identification, Characterization, and Expression Analysis of Glutamate Receptor-like Gene (GLR) Family in Sugarcane." Plants 11, no. 18 (September 19, 2022): 2440. http://dx.doi.org/10.3390/plants11182440.
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The plant glutamate receptor-like gene (GLR) plays a vital role in development, signaling pathways, and in its response to environmental stress. However, the GLR gene family has not been comprehensively and systematically studied in sugarcane. In this work, 43 GLR genes, including 34 in Saccharum spontaneum and 9 in the Saccharum hybrid cultivar R570, were identified and characterized, which could be divided into three clades (clade I, II, and III). They had different evolutionary mechanisms, the former was mainly on the WGD/segmental duplication, while the latter mainly on the proximal duplication. Those sugarcane GLR proteins in the same clade had a similar gene structure and motif distribution. For example, 79% of the sugarcane GLR proteins contained all the motifs, which proved the evolutionary stability of the sugarcane GLR gene family. The diverse cis-acting regulatory elements indicated that the sugarcane GLRs may play a role in the growth and development, or under the phytohormonal, biotic, and abiotic stresses. In addition, GO and KEGG analyses predicted their transmembrane transport function. Based on the transcriptome data, the expression of the clade III genes was significantly higher than that of the clade I and clade II. Furthermore, qRT-PCR analysis demonstrated that the expression of the SsGLRs was induced by salicylic acid (SA) treatment, methyl jasmonic acid (MeJA) treatment, and abscisic acid (ABA) treatment, suggesting their involvement in the hormone synthesis and signaling pathway. Taken together, the present study should provide useful information on comparative genomics to improve our understanding of the GLR genes and facilitate further research on their functions.
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Wang, Hongchen, Qiuyi Chen, Shizhu Zhang, and Ling Lu. "A Transient Receptor Potential-like Calcium Ion Channel in the Filamentous Fungus Aspergillus nidulans." Journal of Fungi 7, no. 11 (October 28, 2021): 920. http://dx.doi.org/10.3390/jof7110920.
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Transient Receptor Potential (TRP) proteins constitute a superfamily that encodes transmembrane ion channels with highly diverse permeation and gating properties. Filamentous fungi possess putative TRP channel-encoded genes, but their functions remain elusive. Here, we report that a putative TRP-like calcium channel, trpR, in the filamentous fungus Aspergillus nidulans, performs important roles in conidiation and in adapting to cell wall disruption reagents in a high temperature-induced defect-dependent manner, especially under a calcium-limited culture condition. The genetic and functional relationship between TrpR and the previously identified high-affinity calcium channels CchA/MidA indicates that TrpR has an opposite response to CchA/MidA when reacting to cell wall disruption reagents and in regulating calcium transients. However, a considerable addition of calcium can rescue all the defects that occur in TrpR and CchA/MidA, meaning that calcium is able to bypass the necessary requirement. Nevertheless, the colocalization at the membrane of the Golgi for TrpR and the P-type Golgi Ca2+ ATPase PmrA suggests two channels that may work as ion transporters, transferring Ca2+ from the cytosol into the Golgi apparatus and maintaining cellular calcium homeostasis. Therefore, combined with data for the trpR deletion mutant revealing abnormal cell wall structures, TrpR works as a Golgi membrane calcium ion channel that involves cell wall integration.
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Ghosh, Soma, Malathi Bheri, and Girdhar K. Pandey. "Delineating Calcium Signaling Machinery in Plants: Tapping the Potential through Functional Genomics." Current Genomics 22, no. 6 (December 30, 2021): 404–39. http://dx.doi.org/10.2174/1389202922666211130143328.
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: Plants have developed calcium (Ca2+) signaling as an important mechanism of regulation of stress perception, developmental cues, and responsive gene expression. The post-genomic era has witnessed the successful unravelling of the functional characterization of genes and the creation of large datasets of molecular information. The major elements of Ca2+ signaling machinery include Ca2+ sensors and responders such as Calmodulins (CaMs), Calmodulin-like proteins (CMLs), Ca2+/CaM-dependent protein kinases (CCaMKs), Ca2+-dependent protein kinases (CDPKs), Calcineurin B-like proteins (CBLs) as well as transporters, such as Cyclic nucleotide-gated channels (CNGCs), Glutamate-like receptors (GLRs), Ca2+-ATPases, Ca2+/H+ exchangers (CAXs) and mechanosensitive channels. These elements play an important role in the regulation of physiological processes and plant responses to various stresses. Detailed genomic analysis can help us in the identification of potential molecular targets that can be exploited towards the development of stress-tolerant crops. The information sourced from model systems through omics approaches helps in the prediction and simulation of regulatory networks involved in responses to different stimuli at the molecular and cellular levels. The molecular delineation of Ca2+ signaling pathways could be a stepping stone for engineering climate-resilient crop plants. Here, we review the recent developments in Ca2+ signaling in the context of transport, responses, and adaptations significant for crop improvement through functional genomics approaches.
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Congar, Patrice, Annie Bergevin, and Louis-Eric Trudeau. "D2 Receptors Inhibit the Secretory Process Downstream From Calcium Influx in Dopaminergic Neurons: Implication of K+ Channels." Journal of Neurophysiology 87, no. 2 (February 1, 2002): 1046–56. http://dx.doi.org/10.1152/jn.00459.2001.
Full textAbstract:
Dopaminergic (DAergic) neurons possess D2-like somatodendritic and terminal autoreceptors that modulate cellular excitability and dopamine (DA) release. The cellular and molecular processes underlying the rapid presynaptic inhibition of DA release by D2 receptors remain unclear. Using a culture system in which isolated DAergic neurons establish self-innervating synapses (“autapses”) that release both DA and glutamate, we studied the mechanism by which presynaptic D2 receptors inhibit glutamate-mediated excitatory postsynaptic currents (EPSCs). Action-potential evoked EPSCs were reversibly inhibited by quinpirole, a selective D2 receptor agonist. This inhibition was slightly reduced by the inward rectifier K+ channel blocker barium, largely prevented by the voltage-dependent K+channel blocker 4-aminopyridine, and completely blocked by their combined application. The lack of a residual inhibition of EPSCs under these conditions argues against the implication of a direct inhibition of presynaptic Ca2+ channels. To evaluate the possibility of a direct inhibition of the secretory process, spontaneous miniature EPSCs were evoked by the Ca2+ ionophore ionomycin. Ionomycin-evoked release was insensitive to cadmium and dramatically reduced by quinpirole, providing evidence for a direct inhibition of quantal release at a step downstream to Ca2+ influx through voltage-dependent Ca2+ channels. Surprisingly, this effect of quinpirole on ionomycin-evoked release was blocked by 4-aminopyridine. These results suggest that D2 receptor activation decreases neurotransmitter release from DAergic neurons through a presynaptic mechanism in which K+ channels directly inhibit the secretory process.
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Ribeiro, Deidiane Elisa, Aline Lulho Roncalho, Talita Glaser, Henning Ulrich, Gregers Wegener, and Sâmia Joca. "P2X7 Receptor Signaling in Stress and Depression." International Journal of Molecular Sciences 20, no. 11 (June 6, 2019): 2778. http://dx.doi.org/10.3390/ijms20112778.
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Stress exposure is considered to be the main environmental cause associated with the development of depression. Due to the limitations of currently available antidepressants, a search for new pharmacological targets for treatment of depression is required. Recent studies suggest that adenosine triphosphate (ATP)-mediated signaling through the P2X7 receptor (P2X7R) might play a prominent role in regulating depression-related pathology, such as synaptic plasticity, neuronal degeneration, as well as changes in cognitive and behavioral functions. P2X7R is an ATP-gated cation channel localized in different cell types in the central nervous system (CNS), playing a crucial role in neuron-glia signaling. P2X7R may modulate the release of several neurotransmitters, including monoamines, nitric oxide (NO) and glutamate. Moreover, P2X7R stimulation in microglia modulates the innate immune response by activating the NLR family pyrin domain containing 3 (NLRP3) inflammasome, consistent with the neuroimmune hypothesis of MDD. Importantly, blockade of P2X7R leads to antidepressant-like effects in different animal models, which corroborates the findings that the gene encoding for the P2X7R is located in a susceptibility locus of relevance to depression in humans. This review will discuss recent findings linked to the P2X7R involvement in stress and MDD neuropathophysiology, with special emphasis on neurochemical, neuroimmune, and neuroplastic mechanisms.
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Carlson, Noel G., Whitney A. Wieggel, Jian Chen, Annalisa Bacchi, Scott W. Rogers, and Lorise C. Gahring. "Inflammatory Cytokines IL-1α, IL-1β, IL-6, and TNF-α Impart Neuroprotection to an Excitotoxin Through Distinct Pathways." Journal of Immunology 163, no. 7 (October 1, 1999): 3963–68. http://dx.doi.org/10.4049/jimmunol.163.7.3963.
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Abstract The proinflammatory cytokines IL-1α, IL-1β, IL-6, and TNF-α are produced within the CNS, and, similar to the periphery, they have pleotrophic and overlapping functions. We have shown previously that TNF-α increases neuronal survival to a toxic influx of calcium mediated through neuronal N-methyl-d-aspartic acid (NMDA) glutamate-gated ion channels. This process, termed excitotoxicity, is a major contributor to neuronal death following ischemia or stroke. Neuroprotection by this cytokine requires both activation of the p55/TNF receptor type I and the release of TNF-α from neurons, and it is inhibited by the plant alkaloid nicotine. Here, we report that other inflammatory cytokines (IL-1α, IL-1β, and IL-6) are also neuroprotective to excessive NMDA challenge in our system. Neuroprotection provided by IL-1 is distinct from TNF-α because it is inhibited by IL-1 receptor antagonist; it is not antagonized by nicotine, but it is inhibited by a neutralizing Ab to nerve growth factor (NGF). Similar to IL-1, IL-6-mediated neuroprotection is also antagonized by pretreatment with IL-1 receptor antagonist and it is not affected by nicotine. However, neutralizing anti-NGF only partially blocks IL-6-mediated protection. These studies support an important role for distinct but overlapping neuroprotective cytokine effects in the CNS.
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Lai, F., C. X. Chen, K. C. Carter, and K. Nishikura. "Editing of glutamate receptor B subunit ion channel RNAs by four alternatively spliced DRADA2 double-stranded RNA adenosine deaminases." Molecular and Cellular Biology 17, no. 5 (May 1997): 2413–24. http://dx.doi.org/10.1128/mcb.17.5.2413.
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Double-stranded (ds) RNA-specific adenosine deaminase converts adenosine residues into inosines in dsRNA and edits transcripts of certain cellular and viral genes such as glutamate receptor (GluR) subunits and hepatitis delta antigen. The first member of this type of deaminase, DRADA1, has been recently cloned based on the amino acid sequence information derived from biochemically purified proteins. Our search for DRADA1-like genes through expressed sequence tag databases led to the cloning of the second member of this class of enzyme, DRADA2, which has a high degree of sequence homology to DRADA1 yet exhibits a distinctive RNA editing site selectivity. There are four differentially spliced isoforms of human DRADA2. These different isoforms of recombinant DRADA2 proteins, including one which is a human homolog of the recently reported rat RED1, were analyzed in vitro for their GluR B subunit (GluR-B) RNA editing site selectivity. As originally reported for rat RED1, the DRADA2a and -2b isoforms edit GluR-B RNA efficiently at the so-called Q/R site, whereas DRADA1 barely edits this site. In contrast, the R/G site of GluR-B RNA was edited efficiently by the DRADA2a and -2b isoforms as well as DRADA1. Isoforms DRADA2c and -2d, which have a distinctive truncated shorter C-terminal structure, displayed weak adenosine-to-inosine conversion activity but no editing activity tested at three known sites of GluR-B RNA. The possible role of these DRADA2c and -2d isoforms in the regulatory mechanism of RNA editing is discussed.
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Blanton, M. G., and A. R. Kriegstein. "Properties of amino acid neurotransmitter receptors of embryonic cortical neurons when activated by exogenous and endogenous agonists." Journal of Neurophysiology 67, no. 5 (May 1, 1992): 1185–200. http://dx.doi.org/10.1152/jn.1992.67.5.1185.
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1. The properties of receptors for amino acid neurotransmitters expressed by developing cortical neurons were studied with the use of whole-cell recording in the intact cerebral cortex of embryonic turtles in vitro. The inhibitory agonist gamma-aminobutyric acid (GABA) and the excitatory agonist glutamate were focally applied to single cells under voltage clamp, and the ionic dependence, voltage dependence, and pharmacological sensitivity of the responses were characterized. The responses mediated by a glutamate receptor subtype, the N-methyl-D-aspartate (NMDA) receptor, produced by glutamate and by evoked release of an endogenous excitatory agonist, were compared further. Fluctuation analysis was used to characterize the properties of the NMDA channels and the mechanism of action of receptor antagonists. 2. When postmitotic neurons first appeared at stage 15, all neurons tested responded to GABA with a current that reversed at the equilibrium potential for chloride ions and that was sensitive to the GABAA receptor antagonist bicuculline methiodide (BMI). As development proceeded, an increasing proportion of neurons also responded with a BMI-insensitive current that reversed near the equilibrium potential for potassium ions. This current was blocked by the GABAB receptor antagonist 3-amino-2-propyl phosponic acid (phaclofen). The GABAB agonist baclofen, however, failed to produce a detectable postsynaptic current. 3. Neurons at stage 15 showed a biphasic response to glutamate that reversed at the equilibrium potential for cations. All neurons tested showed a slow, sustained response associated with an increase in current variance compared with background, and, as development proceeded, an increasing proportion also exhibited a fast, transient response. Both fast and slow responses varied linearly with voltage in the absence of Mg2+ ions, but the addition of Mg2+ ions to the bathing medium attenuated the slow response at hyperpolarized potentials. As a result, the current-voltage relation of the slow response in the presence of Mg2+ ions exhibited a region of negative slope conductance, like that of currents mediated by NMDA receptors. 4. The fast and slow responses to glutamate differed in their pharmacological sensitivity. The fast responses were sensitive to the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), whereas the slow responses were sensitive to the NMDA receptor antagonist D(-)-2-amino-5-phosphonovalerate (D-APV). 5. When cells were held at -70 mV, glutamate evoked a fluctuating current consisting of channel currents with a mean open time, tau, of 4.42 +/- 0.47 (SE) ms in early postmitotic neurons at stage 15 and 4.99 +/- 0.38 ms at stages 17-20.(ABSTRACT TRUNCATED AT 400 WORDS)