Tesis sobre el tema "?-arrestin"
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Sharmeen, Cynthia. "Involvement of Beta-arrestin 1 and Beta-arrestin 2 in store operated calcium entry". Mémoire, Université de Sherbrooke, 2016. http://hdl.handle.net/11143/9499.
Texto completoAbstract : In an organism, intracellular [Ca2+] takes part in many biological processes. Eukaryotic cells express a variety of channels in the plasma membrane through which calcium can enter. In non-excitable cells, two main mechanisms allow calcium entry; the store-operated calcium entry via Orai1 (SOCE) and receptor-operated calcium entry (ROCE). Several key proteins are involved in the regulation of these calcium entry pathways as well as in calcium homeostasis. TRPC6 is a calcium channel implied in calcium entrance into the cells following hormonal stimulation and translocates to the plasma membrane. TRPC6 channel appear to the plasma membrane until the stimulus is present. Although, the mechanisms that regulate the trafficking and activation of TRPC6 are still little known. Recent findings have demonstrated that there is a potential role of Rho kinase in activity of TRPC6. Rho kinase is activated by the small G protein RhoA that itself can be activated by the heterotrimeric G proteins Gα12 and Gα13. In addition to Gα12 and Gα13 proteins, cytosolic GPCR desensitizing proteins β-arrestin 1 and/or β-arrestin 2 could also activate RhoA. The purpose of our study is to investigate the involvement of the proteins Gα12/13 and β-arrestin 1/β-arrestin 2 in the activation of TRPC6 and Orai1 protein. We used siRNA specific to Gα12/13 or β-arrestin 1/β-arrestin 2 to knockdown their endogenous expression. Then, calcium imaging in real time was performed in order to see the quantity of calcium entered into the cell following stimulation by vasopressin (AVP), thapsigargin, or carbachol. We hence identified that in A7r5 cell, vascular smooth muscle cell where TRPC6 channel expressed endogenously; reduced expression of Gα12 or Gα13 proteins does not seem to modify the AVP-induced Ca2+ entry compared to control cells. On the other hand, calcium imaging experiment in knocked down β-arrestin 1 or β-arrestin 2 in HEK 293 cells as well as HEK 293 cells stably transfected with TRPC6 (T6.11 cells) resulted in an increased thapsigargin-induced calcium entry. The co-immunoprecipitation studies demonstrate an interaction between β-arrestin 1 and STIM1, a calcium sensor in SOCE influx, while no interaction was observed between β-arrestin 1 and Orai1.We moreover showed by confocal microscopy that reduced expression of β-arrestin 1/ β-arrestin 2 does not influence the quantity of Orai1 at the cell periphery. Preliminary results showed that reduced expression of β-arrestin 1 or β-arrestin 2 increases the quantity of STIM1-YFP in the intracellular space and less it’s in peri-membrane space. In conclusion, we showed that β-arrestin 1 or β-arrestin 2 are involved in the store-operated calcium entry (SOCE) and control the quantity of STIM1 in the endoplasmic reticulum.
Saxena, Kunal. "Arrestin interactions with the μ-opioid receptor". Thesis, University of Bristol, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.559233.
Texto completoCarter, Alison A. "Molecular pharmacology of agonist-stimulated arrestin-receptor interactions". Thesis, University of Nottingham, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.440126.
Texto completoEidhoff, Ulf Benno. "Heterologe Expression, Kristallisation und Untersuchungen zur Struktur von Bos taurus [beta]-Arrestin-1 [Beta-Arrestin-1] und Rattus norvegicus PAR-4". [S.l. : s.n.], 2000. http://deposit.ddb.de/cgi-bin/dokserv?idn=961407883.
Texto completoCorrell, Jennifer A. "Nicotine Sensitization in β-Arrestin 2 Knockout Adolescent Mice". Digital Commons @ East Tennessee State University, 2007. https://dc.etsu.edu/etd/2050.
Texto completoLally, Ciara. "Structural and functional characterization of the arrestin-rhodopsin complex". Doctoral thesis, Humboldt-Universität zu Berlin, 2017. http://dx.doi.org/10.18452/18570.
Texto completoThe protein arrestin is responsible for termination of GPCR signalling. In the rod cell, arrestin binds light-activated phosphorylated rhodopsin in order to block further signal transduction. The binding of arrestin to rhodopsin is a two-step process. Arrestin first interacts with the phosphorylated receptor C-terminus in a pre-complex, which induces conformational changes in arrestin that allow coupling to the helical core of the active receptor in a high-affinity complex. Biochemical studies and crystal structures have provided insights into the conformation of the arrestin-rhodopsin complex. This dissertation describes site-directed fluorescence experiments, which were carried out to further investigate the conformational changes occurring upon arrestin binding to rhodopsin and the nature of different binding modes of the arrestin-rhodopsin interaction. In particular this involved characterization of a previously unidentified association of arrestin with the membrane, as well as further elucidation of the structure of the pre-complex. The conformation of arrestin in the pre-complex is indicated to resemble that of the basal state of arrestin, and involves two sites of contact: interaction with the phosphorylated receptor C-terminus, and association with the membrane. Upon transition to the high-affinity complex, arrestin undergoes a conformational change to a more active conformation: the auto-inhibitory C-tail is displaced, there is movement within the central flexible loops, and the orientation of the membrane anchor changes. The pre-complex therefore most likely functions to bring arrestin and the receptor into close contact, and in the correct orientation, to allow for fast transition to the high-affinity complex.
Obeid, Joëlle. "Caractérisation de la fonction des β-arrestines dans les cellules β pancréatiques : recherche de nouvelles stratégies thérapeutiques pour le diabète de type 2". Thesis, Montpellier, 2018. http://www.theses.fr/2018MONTT066.
Texto completoThe loss of function and mass of pancreatic beta-cells play a central role in type 2 diabetes (T2D). Beta-arrestin 1 and 2 (ARRB1 and ARRB2) are involved in insulin secretion and/or beta-cell survival. In a first study, in order to characterize the role of ARRB1 in beta-cells, we aimed to invalidate the Arrb1 gene specifically in these cells using the Cre/lox system under the control of the Ins1 promoter. Studies had been published with both Ins1Cre-/+ and Arrb1f/f lines. We generated Arrb1f/f:Ins1Cre-/+ mice. The phenotype of Arrb1f/f :Ins1Cre-/+ mice was weak with a lack of reproducibility compared to Arrb1f/f :Ins1Cre-/- mice used as controls. The low expression level of Arrb1 in beta-cells and the lack of specific antibody for immunocytochemistry made it difficult to verify the absence of expression of ARRB1 in these cells. After sequencing the modified Arrb1 gene of the “floxed” mice, we observed that the insertion of the first loxP site induced a shift in the reading frame introducing a stop codon and, consequently, the non-expression of the Arrb1 gene. Since the “floxed“ Arrb1 mice used as controls were already knockout (KO), the project using these mice was stopped.Our team has reported the involvement of ARRB2 in the regulation of beta-cell mass, but its role in Glucagon-Like Peptide-1 (GLP-1) receptor signaling, a major therapeutic target for T2D, remained to be explored. In a second study, we showed a better glucose tolerance and an increase in insulin secretion from isolated islets in Arrb2KO compared to control mice in the presence of physiological circulating concentrations of GLP-1. This was correlated with higher cAMP production and PKA activation in Arrb2KO beta-cells. By contrast, the activation of ERK1/2 kinases was decreased indicating a major recruitment of ERK1/2 by ARRB2 to GLP-1R. In parallel, we showed that the expression levels of ARRB1 and ARRB2 in pancreatic islets were altered in diabetogenic and diabetic conditions. My results clearly demonstrate a critical role of ARRB2 in GLP-1R singaling which could impact the function, maintenance and plasticity of beta-cell mass in response to GLP-1. A lack of expression of ARRB2 could participate in the deficit of compensatory mechanisms of the functional beta-cell mass leading to T2D
Puca, Loredana. "Role of the arrestin family in notch pathway in mammals". Paris 6, 2013. http://www.theses.fr/2013PA066350.
Texto completoNotch signaling is an evolutionary conserved pathway implicated in embryonic development and in adult tissue homeostasis. A number of post-translational modifications have been implicated in regulating the activity of Notch receptor and some of them affect the degradation of non-activated Notch receptor. The starting points of my PhD project are Drosophila findings showing that the adaptor protein Kurtz, the unique non-visual arrestin in Drosophila, is an essential regulator of Notch signaling. In mammals the arrestin family (excluding the visual arrestins) is composed of two sub-families: -arrestins and-arrestins. The main results that I have obtained show that both -arrestins and -arrestins are recruited to non-activated Notch receptor and allow Itch-mediated Notch ubiquitination in mammals. Biochemical evidence shows that an heterodimerization between -arrestins and the -arrestin ARRDC1 is required to promote Notch ubiquitination and its lysosomal degradation. To conclude, we show for the first time that the --arrestin heterodimer is functionally involved in the degradation of Notch receptor, highlighting the existence of a cooperation between these adaptor proteins to regulate receptor trafficking
Celver, Jeremy Phillip. "Molecular mechanisms of opioid receptor regulation by GRK and arrestin /". Thesis, Connect to this title online; UW restricted, 2002. http://hdl.handle.net/1773/6299.
Texto completoArmando, Sylvain. "Structure quaternaire des récepteurs de chimiokines CXCR4 et CCR2 et interaction avec leur effecteurs". Thesis, Montpellier 2, 2010. http://www.theses.fr/2010MON20208/document.
Texto completoG protein coupled receptors (GPCR) are the most represented cell surface receptors among vertebrates, and the major therapeutic target in humans. The initial paradigm stating a 1 :1 :1 stoichiometry for receptor :G protein :effector has evolved to a more complex model, as illustrated here with the example of the chemokine receptors CXCR4 and CCR2. Bioluminescence resonance energy transfer (BRET) was used to demonstrate that (1) CXCR4 is able to couple Gα13 instead of Gαi to promote breast cancer metastasis, (2) the multiple pathways engaged by stimulation of CXCR4 are selectively desensitized by the specific recruitment of a defined combination of proteins (GRKs and arrestins) and (3) the CXCR4 protomer plays a crucial role during Gαi engagement and β-arrestin recruitment by the CXCR4/CCR2 heterodimer upon CCR2 activation. In this last and main study, the results shown also demonstrate that CCR2 dimers could assemble with CX CR4 dimers into hetero-tetramers, and that CCR2 activation leads to a conformational change in the CXCR4 dimer. Former results showing cooperativity and asymmetric activation of a simple CXCR4/CCR2 heterodimer could then be applied to a tetramer. To conclude, the work done during this thesis demonstrates a more sophisticated regulation of chemokine receptors than previously suspected at 3 different levels: quaternary structure of the protomers, G protein signalling, and signalling termination
Lee, Kyu Joon. "Molecular Mechanisms of Beta-Arrestin-1 Dependent Regulation of LIMK and Cofilin". Thesis, University of California, Riverside, 2016. http://pqdtopen.proquest.com/#viewpdf?dispub=10109679.
Texto completoBeta-arrestins are adaptor proteins that can scaffold a number of signaling proteins to promote localized activity within the cell. Downstream of some GPCRs, β-arrestins can promote activation of the actin filament severing protein, cofilin, through two mechanisms: one involving inhibition of LIM Kinase (LIMK) which negatively regulates cofilin activity through phosphorylation on serine 3. The mechanism by which β-arrestin-1 regulates LIMK activity has not been elucidated; however, it has been shown to be important for cell migration downstream of protease-activate-receptor-2 (PAR-2), dendritic spine formation and opioid receptor function. Here my work demonstrate that β-arrestin-1 directly binds both cofilin and LIMK, and inhibits LIMK activity directly and investigate the mechanism by which inhibition of kinase activity occurs. Using serial truncations and site-directed mutagenesis, I identify crucial residues for cofilin and LIMK interaction within amino acids 1-99 of β-arrestin-1 and show that charged residues at 50 and 51 are crucial for binding to LIMK and R51 is required for LIMK inhibition, PAR2 stimulated cofilin dephosphorylation and cell migration. Additionally, our work reveals that amino acids 1-99 aminos of β-arrestin-1 bind both cofilin and LIMK with a higher apparent affinity than the full length and blocks PAR2-stimulated cofilin dephosphorylaton in HEK293 cells, suggesting it functions as a selective dominant negative β-arrestin-1, inhibiting specifically the cofilin pathway. Thus, residues in the N-terminus of β-arrestin-1 are involved in LIMK inhibition and cofilin activation and this, in turn, is important for cell migration downstream of PAR-2.
Webb, K. F. "Elucidating an essential role for β-arrestin 1 in regulating Golgi morphology". Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1418064/.
Texto completoVogt, Vivien. "Untersuchungen zur Phosphorylierung von Rhodopsin und deren Einfluss auf die Arrestin-Rhodopsin-Bindung". Doctoral thesis, Humboldt-Universität zu Berlin, 2021. http://dx.doi.org/10.18452/22841.
Texto completoThe phosphorylation-dependent binding of arrestin to G protein-coupled receptors (GPCRs) is a widely used mechanism to inhibit active receptors. In lipid membranes, the binding of arrestin to light-activated, phosphorylated rhodopsin (pRho), a GPCR located in the disc membranes of retinal rod cells, requires the phosphorylation of 2 of the 7 phosphorylation sites in the receptor C-terminus, whereas 3 phosphates are required to completely activate arrestin. The influence of higher phosphorylation levels on the receptor/arrestin interaction is still unclear. In this thesis, a method for the quantitative determination of rhodopsin phosphorylation was established, rhodopsin species with varying degrees of phosphorylation were separated preparatively and different parameters of the receptor/arrestin interaction, such as the binding stoichiometry of the resulting pRho/arrestin complexes, were investigated for each isolated pRho species. For the characterization of arrestin binding, titrations with 3 different fluorescently labeled arrestin mutants and pRho in mixed phospholipid/detergent micelles were performed. The data obtained in this work show that the phosphorylation level of rhodopsin influences the binding stoichiometry in addition to the affinity of arrestin binding to rhodopsin. Thus, complexes with a low level of phosphorylation have a 2 : 1 (pRho : arrestin) stoichiometry, whereas 1 : 1 pRho/arrestin complexes are preferably formed at a very high degree of phosphorylation. In addition, a different elution behaviour during chromatographic separation and variances in the pRho/arrestin stoichiometry of different pRho preparations with similar overall number of phosphates indicate an additional influence of distinct phosphorylation patterns. Overall, the data indicate a complex relationship between receptor phosphorylation level and arrestin binding mode.
Mendez, Martinez-David Indira. "Effets anxiolytiques/antidépresseurs et neurogéniques des ligands du récepteur 5-HT4 chez la Souris : rôle de la protéine β-arrestin 1". Thesis, Paris 11, 2013. http://www.theses.fr/2013PA114843/document.
Texto completoSelective serotonin reuptake inhibitors (SSRIs) display a delayed onset of action of several weeks. Past work demonstrated evidence that the 5-HT4 receptor may be a direct target for treating depression and a new hope for fast acting antidepressant treatment. However, the 5-HT4 hypothesis still needs to be validated in models of anxiety/depression.We decided to investigate whether 5-HT4 receptor stimulation was necessary for the effects of SSRIs in a mouse model of anxiety/depression and whether hippocampal neurogenesis contributed to these effects. Using the mouse corticosterone model of anxiety/depression, we assessed whether chronic treatment with a 5-HT4 receptor agonist (RS67333, 1.5 mg/kg/day) had effects on anxiety and depression-related behaviors as well as on hippocampal neurogenesis in comparison to chronic fluoxetine treatment (18 mg/kg/day). Then, using our model combined with ablation of hippocampal neurogenesis, we investigated whether neurogenesis was necessary for the behavioral effects of subchronic (7-days) or chronic (28-days) RS67333 treatment. We also assessed whether a 5-HT4 receptor antagonist, (GR125487, 1 mg/kg/day) could prevent the behavioral and neurogenic effects of fluoxetine. Chronic treatment with RS67333, similar to fluoxetine, induced anxiolytic/antidepressant-like activity and stimulated adult hippocampal neurogenesis. However, unlike fluoxetine, the anxiolytic effects of RS67333 were already present after 7 days and did not require hippocampal neurogenesis. Chronic treatment with GR125487 prevented both anxiolytic/antidepressant-like and neurogenic effects of fluoxetine, indicating that 5-HT4 receptor activation is necessary for these effects of SSRIs. We then explored whether the fast onset of action of the 5-HT4 receptor agonist RS67333 could be predicted by expression of a peripheral biomarker. The β-arrestin-signaling cascade which is involved in 5-HT4 receptor desensitization and internalization, has recently gained attention as a potential pre-clinical/clinical bridging biomarker for depressive states and treatment effects. To this end, we developed a new method to assess levels of circulating proteins through immunoblot analyses of mouse PBMCs isolated from whole blood of anesthetized animals. While we did not detect any change in β-arrestin 1 in mouse leukocytes after 7 days of fluoxetine in corticosterone-treated animals, a short term treatment with RS67333, restored the level of this protein to control levels. In fluoxetine-treated animals, a restoration was only observed in the corticosterone model after a longer exposure. These results suggest that blood levels of β-arrestin 1 may be a useful biomarker to predict antidepressant/anxiolytic activities. Finally, the activation of 5-HT4 receptors in the brain may represent an innovative and rapid onset therapeutic approach to treat depression with comorbid anxiety
Groer, Chad E. "Agonist-selective regulation of the mu opioid receptor by βarrestins". The Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1284396146.
Texto completoNkwayana, Nonhlanhla. "β-arrestin interacting domains on the type II gonadotropin-releasing hormone (GnRH) receptor". Master's thesis, University of Cape Town, 2006. http://hdl.handle.net/11427/3178.
Texto completoIncludes bibliographical references.
Includes bibliographical references (leaves 74-81).
Over-expression of β-arrestin 1 in COS-l cells revealed that the mammalian type GnRH receptor can internalise in a β-arrestin dependent manner whereas the internalisation of the mammalian type I GnRH receptor is β-arrestin independent. investigate which domains on the mammalian type II GnRH receptor are required for β~arrestin dependent internalisation, chimeric receptors were created.
The mammalian type II GnRH receptor possesses an intracellular C-terminal tail that is known to play a role in desensitisation, internalisation and overall signalling in GPCRs. On the other hand, the mammalian type I GnRH receptor, which lacks a C-terminal tail, does not readily desensitise and undergoes slow internalisation compared to the mammalian type II GnRH receptor. Over-expression of ß-arrestin 1 in COS-l cells revealed that the mammalian type GnRH receptor can internalise in a ß-arrestin dependent manner whereas the internalisation of the mammalian type I GnRH receptor is ß-arrestin independent. investigate which domains on the mammalian type II GnRH receptor are required for ß-arrestin dependent internalisation, chimeric receptors were created. Firstly, a chimera in which the full length type II GnRH receptor C-terminal tail was added to the tail-less type I GnRH receptor (TI/T2tail) was created. This chimera internalised in a ß-arrestin and GRK dependent manner, demonstrating that the type II GnRH receptor C-terminal tail confers ß-arrestin JGRK dependent internalisation on the originally ß-arrestin/GRK insensitive GnRH receptor. Mutating the putative GRK and casein kinase phosphorylation sites (serines 338 and 339) on the C-terminal tail of TI/T2tail to alanine residues did not abolish ß-arrestin dependent internalisation but eliminated GRK dependent internalisation, suggesting that other regions on the C-terminal tail are required for ß-arrestin dependent internalisation. A second chimera, in which the whole third intracellular loop of the type II GnRH receptor was replaced with that of the type I GnRH receptor (T2/TIICL3), was created. This chimera could not utilise ß-arrestin in its internalisation, indicating that the third intracellular loop of the type II GnRH receptor is required for ß-arrestin dependent internalisation. An alignment of the amino acid sequences of the two mammalian GnRH receptor third intracellular loops identified a basic residue rich area (R234, R236 and K237) on the type II GnRH receptor that was absent on the type I GnRH receptor. Interestingly, the triple mutant (R234,236,K237 A) still internalised in a ß-arrestin dependent manner, however, truncation of the C-terminal tail of R234,236,K237A abolished the ability of the receptor to internalise in a ß-arrestin dependent manner. This result indicated that the C-terminal tail of the type II GnRH receptor was compensating for the absence of the three basic residues. To summarise, this thesis demonstrates that the C-terminal tail of the type II GnRH receptor can confer ß-arrestin dependent intemalisation on the type I GnRH receptor. Furthermore, the third intracellular loop, and more specifically, basic residues R234, R236 and K237 on the mammalian type II GnRH receptor are required for ß-arrestin dependent intemalisation.
Jones, Kymry Thereasa. "The role of beta-arrestin in regulating the muscarinic acetylcholine type II receptor". Diss., Atlanta, Ga. : Georgia Institute of Technology, 2007. http://hdl.handle.net/1853/24815.
Texto completoCommittee Chair: Dr. Nael A. McCarty; Committee Co-Chair: Dr. Darrell Jackson; Committee Member: Dr. Alfred H. Merrill; Committee Member: Dr. Barbara D. Boyan; Committee Member: Dr. Harish Radhakrishna; Committee Member: Dr. Marion B. Sewer
Cancellieri, C. "BETA-ARRESTIN DEPENDENT REGULATION OF CYTOSKELETON DYNAMICS AND SIGNALLING OF CHEMOKINE RECEPTOR ACKR2". Doctoral thesis, Università degli Studi di Milano, 2014. http://hdl.handle.net/2434/229565.
Texto completoDarcet, Flavie. "Rôle du récepteur 5-HT4 et de la protéine beta-arrestine 1 dans la modulation des processus émotionnels et cognitifs dans un modèle d'anxiété-dépression". Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS126/document.
Texto completoCognitive disturbances are often reported as serious incapacitating symptoms by patients suffering from major depressive disorders. Recent studies showed that these mood disorders could benefit from the modulation of 5-HT4 receptor pathway. Here, we performed a complete characterization of cognitive functions in a neuroendocrine mouse model of depression, the CORT model. We then evaluated emotional and cognitive effects of either a chronic 5-HT4 receptor agonist treatment, RS 67333 or fluoxetine, a classical monoaminergic antidepressant. Recent data indicate that β-arrestins proteins could be an important molecular determinant in depressive states and in the effects of antidepressants. We determined emotional and cognitive phenotypes in conditional tissue-specific mice in which expression of β-arrestin 1 in adult hippocampal stem cells was deleted. This work suggests that the 5-HT4 receptor plays a major role to correct not only anxiety/depression-related symptoms but also cognitive alterations in a mouse model of anxiety/depression model. Moreover, these data confirm the involvement of β-arrestin 1 protein in behavioral and neurogenic responses to fluoxetine treatment in adult mice. Finally, β-arrestin 1 protein expression in adult born neuron is critical for cognition and also to fluoxetine and RS 67333 response
Wilham, Laura Elizabeth. "The role of [beta]-arrestin in agonist-induced down-regulation of the M₁mAChR". CONNECT TO THIS TITLE ONLINE, 2006. http://etd.lib.umt.edu/theses/available/etd-03022007-104437/.
Texto completoHabourdin, Clemence. "Caractérisation des membres du clan arrestine chez l'amibe Dictyostelium discoideum : Etude de la protéine AdcA et de son partenaire FrmC". Thesis, Grenoble, 2014. http://www.theses.fr/2014GRENV074/document.
Texto completoThe arrestin clan represents a large group of adaptor proteins which includes the canonical arrestins - β-arrestins and visual arrestins – well described for their role in the regulation of membrane receptors coupled to heterotrimeric G-proteins and associated signaling as well as arrestin-like proteins identified more recently that seem to share functions in the regulation and trafficking of membrane cargoes. This work focused on the study of the arrestin-like protein AdcA of Dictyostelium discoideum, to determine the functional role of this atypical member. In addition to the arrestin module common to all the members of the arrestin family, AdcA harbors a FYVE domain responsible for its association to the endocytic pathway, a C-terminal tyrosine-rich domain and an N-terminal extension rich in histidine residues mediating its oligomerization. I have established that AdcA responds to a variety of stresses such as hyperosmolarity by a massive multi-phosphorylation of the protein. Sensitivity of AdcA to changes in F-actin polymerization status suggests a link between the signaling cascade leading to AdcA phosphorylation and the actin cytoskeleton. In conditions of moderate stress, AdcA response is transient and its dephosphorylation depends on the transcription factor STATc and correlates with cell adaptation to the stress conditions. This post-translational modification of AdcA could modulate its activity and optimitize the cell response to stress. In parallel, the functional characterization of a partner of AdcA, the protein FrmC, has been undertaken. This so-far uncharacterized protein presents a multimodular structure with a FERM domain able to bind F-actin in vitro and several leucine-rich repeats (LRR). I have shown that FrmC is recruited to the plasma membrane and is involved in cell-substrate adhesion. In addition, disruption of FrmC affects cell adaptation and AdcA response in conditions of hyperosmotic stress
Clayton, Ashley Rebecca. "Investigation of the role of SASH1 in the regulation of TRAF6-beta-arrestin complex formation". Thesis, University of British Columbia, 2014. http://hdl.handle.net/2429/48602.
Texto completoMedicine, Faculty of
Medicine, Department of
Experimental Medicine, Division of
Graduate
Vogt, Vivien [Verfasser]. "Untersuchungen zur Phosphorylierung von Rhodopsin und deren Einfluss auf die Arrestin-Rhodopsin-Bindung / Vivien Vogt". Berlin : Humboldt-Universität zu Berlin, 2021. http://d-nb.info/1233678582/34.
Texto completoVogt, Viola [Verfasser]. "Effekte chemisch induzierter β-Arrestin-1-Translokation an die Chemokinrezeptoren CXCR4 und CCR5 / Viola Vogt". Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2021. http://d-nb.info/1238345557/34.
Texto completoGillis, Alexander. "µ-opioid receptor ligand pharmacology in cell and animal models". Thesis, University of Sydney, 2020. https://hdl.handle.net/2123/23113.
Texto completoCarrat, Gaëlle. "La voie de signalisation ERK1/2 couplée au récepteur 5-HT4 et sa régulation par GRK5". Thesis, Montpellier 2, 2010. http://www.theses.fr/2010MON20187/document.
Texto completoG protein-coupled receptors (GPCRs) have been found to trigger G protein-independent signalling. However, the regulation of G protein-independent pathways, especially their desensitization, is poorly characterized.The 5-Hydroxytryptamine 4 receptor (5-HT4R) is a GPCR widely expressed in the brain and at the periphery. It is implicated in important physiological functions such as memory, cognition, feeding, respiratory control and gastrointestinal motility. 5-HT4R couples to the Gs/cAMP/PKA pathway. Moreover, this receptor can activate a Src/ERK pathway independently of both G proteins and β-arrestins.Here, we show that the G protein-independent 5-HT4R-operated Src/ERK pathway, but not the Gs pathway, is inhibited by GPCR kinase 5 (GRK5), physically associated with the proximal region of receptor C-terminus, in both HEK-293 cells and colliculi neurons. This inhibition requires two sequences of events: the association of β-arrestin1 to a phosphorylated serine/threonine cluster located within the receptor C-terminal domain and the phosphorylation by GRK5 of β-arrestin1 (at Ser 412) bound to the receptor. Phosphorylated β-arrestin1 prevents in turn activation of Src constitutively bound to 5-HT4R, a necessary step in receptor-stimulated ERK signalling. This is the first demonstration that β-arrestin phosphorylation by a GRK regulates G protein-independent signalling.In addition to these results, we also demonstrated that the β-arrestin-independent activation of ERK1/2 by the 5-HT4R involves a metalloprotease-dependant ectodomain shedding and transactivation of another receptor. By a proteomic approach, we also identified several potential partners of the 5-HT4R. Study of these proteins may provide a better understanding of 5-HT4R signalling and his regulation
Goh, Poh. "Roles of protein kinase C and arrestin in migration of cells via CXCR4/CXCL12 signalling axis". Thesis, University of East Anglia, 2018. https://ueaeprints.uea.ac.uk/67806/.
Texto completoCorrell, Jennifer A., Daniel M. Noel, A. Brianna Sheppard, Kimberly N. Thompson, Yi Li, Deling Yin y Russell W. Brown. "Nicotine Sensitization and Analysis of Brain-Derived Neurotrophic Factor in Adolescent Beta-Arrestin-2 Knockout Mice". Digital Commons @ East Tennessee State University, 2009. https://doi.org/10.1002/syn.20625.
Texto completoMößlein, Nadja [Verfasser] y Moritz [Akademischer Betreuer] Bünemann. "Untersuchungen zu Mechanismen der Co-Internalisierung von Arrestin-3 mit GPCRs / Nadja Mößlein ; Betreuer: Moritz Bünemann". Marburg : Philipps-Universität Marburg, 2021. http://d-nb.info/1240383878/34.
Texto completoSantos, Ana Paula Carneiro dos. "Participação da via de sinalização da beta-arrestina na produção de óxido nítrico induzido pelo shear stress". Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/5/5166/tde-01042015-150141/.
Texto completoEndothelial cells are capable of converting mechanical stimuli into intracellular signals generating vasoactive factors such as nitric oxide (oNO). Recent evidence suggests that beta-arrestins play a role not only on G protein-coupled receptors (GPCR) desensibilization but also in mechanotransduction. We tested the hypothesis that beta-arrestin and its downstream signaling influence laminar shear stress (SS)-induced oNO production by endothelial cells. Towards this end, human saphenous vein endothelial cells (hSVEC) transfected with siRNA against beta-arrestins isoforms 1 and 2 were subjected to SS (15 dynes/cm2, 10 minutes). We found that the SS-induced production of nitrite in the cell culture medium from down-expressed beta-arrestin 1/ 2 (70%) SVEC decreased (166±17 vs. 326±44% compared to wild-type hSVEC; P < 0.001). The beta-arrestin 1 and 2 down-regulation in SVEC also inhibited the phosphorylation levels of Akt at the serine residue 473 and the phosphorylation levels of eNOS at the serine residue 1177, whereas ERK phosphorylation remained unchanged. Interestingly, immunoprecipitation analysis showed that beta-arrestin interacts with caveolin-1, a shear stress mechanosensor, which is not influenced by SS despite the fact that the static perinuclear localization of beta-arrestins changed to the cytosol upon SS. Collective these data suggest that beta-arrestin and Akt/eNOS downstream signaling are required for shear stress-induced nitric oxide production in human vascular endothelial cells
Beyrière, Florent [Verfasser], Klaus Peter [Akademischer Betreuer] Hofmann y Peter [Akademischer Betreuer] Hildebrandt. "Spectroscopic and microscopic analysis of arrestin-rhodopsin interactions / Florent Beyrière. Gutachter: Peter Hildebrandt. Betreuer: Klaus Peter Hofmann". Berlin : Technische Universität Berlin, 2015. http://d-nb.info/1067388826/34.
Texto completoSeitz, Katharina [Verfasser] y Alexandra [Akademischer Betreuer] Schambony. "Funktionelle Charakterisierung des Frizzled-Dishevelled-Arrestin Komplexes in Frizzled abhängigen Wnt-Signalwegen / Katharina Seitz. Betreuer: Alexandra Schambony". Erlangen : Universitätsbibliothek der Universität Erlangen-Nürnberg, 2012. http://d-nb.info/102636535X/34.
Texto completoZimmerman, Brandon. "Regulation of angiotension II type I receptor signalling by beta-arrestin and the clathrin adaptor AP-2". Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=107645.
Texto completoLes récepteurs couplés aux protéines G (RCPGs) jouent un rôle fondamental dans notre équilibre homéostatique par leur implication dans de nombreux processus physiologiques. Afin de maintenir leur réactivité à l'environnement extracellulaire, un processus complexe de désensibilisation et resensibilisation des récepteurs a évolué. Afin de permettre aux récepteurs d'être resensibilisés, ils doivent d'abord être internalisés par endocytose, un processus impliquant de nombreuses protéines adaptatrices. La méthode la plus commune de l'internalisation des RCPGs est la voie dépendante à la clathrine, où les deux adaptateurs les plus importants sont βarrestine et AP-2. Bien que nous ayons une image relativement claire de la façon dont ces protéines conduisent à l'endocytose du récepteur, les mécanismes de régulation où ces adaptateurs de l'endocytose peuvent affecter ou être affecté par des processus de signalisation sont nettement moins bien décrits. Le récepteur de l'angiotensine II de type I est utilisé comme récepteur modèle dans nos études. Les études antérieures de notre laboratoire ont caractérisé certains des facteurs protéiques nécessaires pour le processus d'endocytose. Bien que les études précédentes ont démontré une régulation dépendante à la phosphorylation des complexes βarrestine et AP-2, ces résultats ont été exclusivement in vitro et n'ont pas été confirmés dans les cellules vivantes. Nous avons généré un anticorps polyclonal dirigé contre le site de phosphorylation putatif et avons révélé que non seulement cet évènement de phosphorylation se produit dans plusieurs types de cellules en réponse au traitement à l'angiotensine II (AngII), mais que l'activation de récepteurs multiples, comprenant un non-RCPG, le récepteur du facteur de croissance de l'épiderme, induisait la phosphorylation sur l'unité β de AP-2. Mon travail, précédemment publié dans un manuscrit, a également révélé que la prévention de cet évènement de phosphorylation stabilise les complexes βarrestine/AP-2 de façon significative. Bien que nos études initiales aient révélé que cette phosphorylation a peu d'impact sur l'endocytose des récepteurs, de nouveaux outils ont depuis été développés dans le laboratoire. Premièrement, nous avons généré un anticorps à chaîne unique qui peut être exprimé de façon intracellulaire et cible les phosphosites, et avons démontré que la liaison à ce résidu phosphorylé résulte dans un arrêt prolongé de l'endocytose. Nous avons également démontré que ce résidu tyrosine phosphorylé est un motif putatif de liaison pour certaines protéines contenant un domaine SH2 étant donné que trois de ces protéines sont capables de se lier à une β2adaptine phosphorylée. Enfin, en raison de la nature dépendate à βarrestine de cet évènement de phosphorylation, nous avons characterise quatre analogies de AngII avec une seule substitution d'acide amine dans leur sequence octapeptidique. Nos conclusions établissent une relation corrélative entre la force d'avidité de βarrestine pour son récepteur et le niveau d'activation de la kinase ERK suite aux signaux extracellulaires. Vraisemblablement, les différences d'avidité modifient le trafic du récepteur dans son destin vers le recyclage ou la dégradation. Par ailleurs, nous établissons que la conformation de βarrestine peut altérer les voies activées en aval du récepteur, entraînant d'autres effets cellulaires comme la croissance cellulaire ou la migration. Ces résultats mettent en évidence l'importance de la régulation par ces adaptateurs de l'endocytose sur le destin du RCPG, non seulement par leur rôle dans l'internalisation, mais aussi par leur propre potentiel de signalisation.
Lake, David Jonathan. "A human alpha-arrestin protein with a potential role in cargo protein trafficking within the endocytic system". Thesis, University of Nottingham, 2013. http://eprints.nottingham.ac.uk/13335/.
Texto completoParisis, Nikolaos. "Identification of PAR-2-regulated ERK substrates and (Beta)-arrestin-interacting proteins in invasive breast cancer cells". Thesis, University of Essex, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.520107.
Texto completoSimard, Élie. "Les β-arrestines et les produits de glycation avancée régulent et modulent respectivement la contraction cellulaire induite par l’activation de récepteurs couplés aux protéines G". Thèse, Université de Sherbrooke, 2015. http://hdl.handle.net/11143/6745.
Texto completoLally, Ciara [Verfasser], Franz [Gutachter] Bartl, Athina [Gutachter] Zouni y Peter [Gutachter] Hegemann. "Structural and functional characterization of the arrestin-rhodopsin complex / Ciara Lally ; Gutachter: Franz Bartl, Athina Zouni, Peter Hegemann". Berlin : Humboldt-Universität zu Berlin, 2017. http://d-nb.info/1189327805/34.
Texto completoFrosch, Clara [Verfasser], Ivo [Gutachter] Quack y Hadi [Gutachter] Al-Hasani. "Die Rolle von β-Arrestin-2 in der hyperglykämieinduzierten Nierenschädigung / Clara Frosch ; Gutachter: Ivo Quack, Hadi Al-Hasani". Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2021. http://d-nb.info/1231541962/34.
Texto completoFelixberger, Johannes [Verfasser] y Armin [Akademischer Betreuer] Buschauer. "Luciferase complementation for the determination of arrestin recruitment: Investigations at histamine and NPY receptors / Johannes Felixberger. Betreuer: Armin Buschauer". Regensburg : Universitätsbibliothek Regensburg, 2016. http://d-nb.info/1082128015/34.
Texto completoZindel, Diana [Verfasser] y Moritz [Akademischer Betreuer] Brünemann. "Die zeitliche Stabilität und zelluläre Lokalisation von Arrestin-Rezeptorkomplexen wird durch die Rezeptorphosphorylierung determiniert. / Diana Zindel. Betreuer: Moritz Brünemann". Marburg : Philipps-Universität Marburg, 2016. http://d-nb.info/108237735X/34.
Texto completoDoan, Thuy Anh. "Mammalian rod's single-photon responses : what do they tell us about rapid and reliable GPCR inactivation /". Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/10638.
Texto completoHirata, Cristiane Lumi. "Thioredoxin interacting protein (Txnip) forms redox sensitive high molecular weight nucleoprotein complexes". Doctoral thesis, Kyoto University, 2021. http://hdl.handle.net/2433/264647.
Texto completoRaehal, Kirsten Michele. "Opioid-Induced Side Effects in Beta-arrestin2 adn G Protein-Coupled Receptor Kinase Knockout Mice". The Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1236884585.
Texto completoFessart, Delphine. "Regulation of the endocytic adaptor proteins [beta] arrestin and AP-2 during clathrin-mediated internalization of Angiotensin II type 1 receptor". Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=102501.
Texto completoThe internalization of Angiotensin II (Ang II) type 1 receptor (AT1R) is controversial and poorly described. Therefore, our laboratory studies the mechanisms behind AT1R internalization. The agonist-induced internalization of AT1R begins with the formation of a complex including betaarrestin, the clathrin adaptor AP-2, and the tyrosine protein kinase, c-Src. In turn, this c-Src recruitment regulates the clathrin-mediated internalization of AT1R by controlling the formation of endocytic complexes during endocytosis. Indeed, the recruitment of c-Src is involved in the dissociation of AP-2 during receptor internalization. Based on our evidence that AP-2 and c-Src can be found in the same complex, we suggested that AP-2 could be phosphorylated by c-Src. Indeed, we found that Ang II induced the c-Src-mediated tyrosine phosphorylation of the beta-subunit of AP-2 (beta2-adaptin). We were able to map one of the tyrosines in beta2-adaptin and assess its role in regulating the binding of its principal partner: betaarrestin. The phosphorylation state of beta2-adaptin dictates its association profile with betaarrestin: when phosphorylated it reduces its binding to betaarrestin. Finally, we proposed a model for AT1R internalization. Overall, these studies are significant because they allow a better understanding of the underlying mechanism that regulates the initial steps of clathrin-coated vesicle endocytosis of AT1R.
David, Indira. "Effets anxiolytiques/antidépresseurs et neurogéniques des ligands du récepteur 5-HT4 chez la Souris : rôle de la protéine β-arrestin 1". Phd thesis, Université Paris Sud - Paris XI, 2013. http://tel.archives-ouvertes.fr/tel-00925063.
Texto completoKilpatrick, Laura Elise. "The use of bimolecular fluorescence complementation (BiFC) to investigate the functional implications of neuropeptide Y receptor dimerisation and beta-arrestin recruitment". Thesis, University of Nottingham, 2015. http://eprints.nottingham.ac.uk/28767/.
Texto completoStorez, Hélène. "Identification de nouveaux partenaires d'interaction des β-arrestines : 1-oligomérisation des β-arrestines : 2-Caractérisation de l'intéraction β-arrestine- Filamine A". Paris 7, 2007. http://www.theses.fr/2007PA077098.
Texto completoβ-arrestins 1 and 2 (BARRIand I3ARR2) are two highly homologous proteins with multiple biological functions. First known as key regulators of G protein-coupled receptor (GPCR) desensitization and endocytosis, βARRs were shown more recently to act as scaffolding proteins for ERK1/2 and JNK3 cascades, to activate Src and to bind to ubiquitin ligases. In addition to their propensity to interact with multiple partners, βARRs might also auto-assemble to form oligomers, as suggested by the observation that both IJARR1 and visual arrestin, the isoform which is specifically expressed in the retina, form dimers in crystals. In a two-hybrid screen, based on the Sos Recruitment System and using a C-terminal truncated mutant of βARR2 as the bait, one of the preys corresponded to the C-terminal portion of βARR2 itself, suggesting that βARR2 might also form dimers in solution. To investigate whether βARR2 might function as a dimer in a more physiological context, we took advantage of the bioluminescence energy transfer (BRET) approach, which was developed recently to study protein-protein interaction in living cells. The cDNAs encoding Renilla luciferase (lue) and the yellow variant of the Green Fluorescent Protein (YFP), the BRET donor and accepter moieties, respectively, were fused 5' or 3' to the cDNAs of βARR1 or βARR2. Various appropriate combinations of the resulting constructs were transfected in COS-7 cells. A constitutive BRET was measured with βARR2 constructs. As expected for a specific non-random interaction between the BRET donor and accepter, BRET signals increased as a function of the BRET accepter concentration up to a maximal value (BRETmax), and constant BRET signals were measured when cells were transfected with increasing amounts of a fixed ratio of acceptordonor. Interestingly, significantly different BRETmax values were measured when the BRET donor construct (βARR2-luc) was co-expressed with fusion proteins in which the BRET accepter was located either at the N-terminal (YFP-βARR2) or the C-terminal (βARR2-YFP) extremity of βARR2, indicating that the βARR-2 dimer is oriented. A similar constitutive BRET was also measured for βARR1 and when the BRET donor and the accepter were fused to different UARRisoforms. These data are consistent with a model in which both βARR2 and βARR1 form constitutive homo-dimers in living cells and might also be engaged in constitutive hetero-dimers. Several important questions are still under investigation, such as the proportion of dimers versus monomers, the effect of GPCR activation on βARR dimerization, the potentially different biological function of monomers, homo-dimers and hetero-dimers
Urs, Nikhil Mahabir. "The regulation of cellular trafficking of the human lysophosphatidic acid receptor 1: identification of the molecular determinants required for receptor trafficking". Diss., Georgia Institute of Technology, 2007. http://hdl.handle.net/1853/16177.
Texto completoPalmer, Erin. "structure activity relationships of melanotropin peptide analogues and elucidation of the contribution of ser/thr phosphorylation in beta -arrestin mediated receptor trafficking". Thesis, The University of Arizona, 2008. http://hdl.handle.net/10150/190696.
Texto completoMekiri, Maryam. "réponse, non-réponse et résistance aux traitements antidépresseurs monoaminergiques. Etude des marqueurs neurogéniques et moléculaires dans un modèle animal d'anxiété-dépression". Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS051/document.
Texto completoAround 30% of patients do not respond adequately to chronic antidepressant treatments. This lack of response, or worsening of the depressive state after the onset of the treatment can lead to treatment resistant depression (TRD). TRD is characterized by a recurrent lack of therapeutic response to various antidepressant which display different mechanism of action. A better understanding of the mechanisms that underlies TRD is necessary to discover some new effective therapeutic strategies. Numerous studies in rodents have shown that chronic antidepressant treatment improves adult hippocampal neurogenesis, and that disrupting this phenomenon partially alters antidepressant response. However whether lack of response or resistance to antidepressant treatment is associated with altered neurogenesis has yet not been observed. Additionally, there is yet no model of TRD with a translational validity. As major depressive disorders affects women twice more than men, yet the preclinical studies are performed mostly in males. Thus, the aim of this thesis was to model non-response an resistance to antidepressant response in male and female C57BL6 mice.The first aim of this thesis work was to induce a anxio-depressive phenotype in female mice, by adapting a neurodencocrine model of depression developed in males and based on chronic administration of corticosterone (CORT). The second aim was to study adult hippocampal neurogenesis in animals that respond or not to chronic fluoxetine administration, and in animals that were resistant to two successive antidepressant treatment with a different mechanism of action (fluoxetine and then imipramine).Additionally, data from the literature suggests that peripheral β-arrestin 1 expression could be a potential biomarker of depressive state and antidepressant response in humans. Thus, we explore its validity in our model of TRD in mice.Overall, our results highlight the difficulty of inducing an anxio-depressive phenotype in female mice, using different dosage or treatment duration of corticosterone, which hampers the use of corticosterone to induce emotionality in female mice.However, in male mice, we showed that we were able model resistance to treatment in the using the CORT model. Lack of response to chronic fluoxetine and treatment resistance to fluoxetine/imipramine were associated with altered neurogenesis in the dentate gyrus of the hippocampus. This confirms that hippocampal neurogenesis is critical for a full antidepressant response. While peripheral β-arrestin 1 expression was not decreased after chronic CORT exposure, its differential expression between responder vs treatment-resistant mice confirms its validity as a biomarker for antidepressant response