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Статті в журналах з теми "Drosophila melanogaster dopamine transporter"

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Автор: Grafiati

Опубліковано: 6 вересня 2023

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1

Pugh, Ciara Frances, Brian Thomas DeVree, Solveig Gaarde Schmidt, and Claus Juul Loland. "Pharmacological Characterization of Purified Full-Length Dopamine Transporter from Drosophila melanogaster." Cells 11, no. 23 (November 28, 2022): 3811. http://dx.doi.org/10.3390/cells11233811.

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The dopamine transporter (DAT) is a member of the neurotransmitter:sodium symporter (NSS) family, mediating the sodium-driven reuptake of dopamine from the extracellular space thereby terminating dopaminergic neurotransmission. Our current structural understanding of DAT is derived from the resolutions of DAT from Drosophila melanogaster (dDAT). Despite extensive structural studies of purified dDAT in complex with a variety of antidepressants, psychostimulants and its endogenous substrate, dopamine, the molecular pharmacology of purified, full length dDAT is yet to be elucidated. In this study, we functionally characterized purified, full length dDAT in detergent micelles using radioligand binding with the scintillation proximity assay. We elucidate the consequences of Na+ and Cl− binding on [3H]nisoxetine affinity and use this to evaluate the binding profiles of substrates and inhibitors to the transporter. Additionally, the technique allowed us to directly determine a equilibrium binding affinity (Kd) for [3H]dopamine to dDAT. To compare with a more native system, the affinities of specified monoamines and inhibitors was determined on dDAT, human DAT and human norepinephrine transporter expressed in COS-7 cells. With our gathered data, we established a pharmacological profile for purified, full length dDAT that will be useful for subsequent biophysical studies using dDAT as model protein for the mammalian NSS family of proteins.

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2

Góral, Izabella, Kamil Łątka, and Marek Bajda. "Structure Modeling of the Norepinephrine Transporter." Biomolecules 10, no. 1 (January 7, 2020): 102. http://dx.doi.org/10.3390/biom10010102.

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The norepinephrine transporter (NET) is one of the monoamine transporters. Its X-ray crystal structure has not been obtained yet. Inhibitors of human NET (hNET) play a major role in the treatment of many central and peripheral nervous system diseases. In this study, we focused on the spatial structure of a NET constructed by homology modeling on Drosophila melanogaster dopamine transporter templates. We further examined molecular construction of primary binding pocket (S1) together with secondary binding site (S2) and extracellular loop 4 (EL4). The next stage involved docking of transporter inhibitors: Reboxetine, duloxetine, desipramine, and other commonly used drugs. The procedure revealed the molecular orientation of residues and disclosed ones that are the most important for ligand binding: Phenylalanine F72, aspartic acid D75, tyrosine Y152, and phenylalanine F317. Aspartic acid D75 plays a key role in recognition of the basic amino group present in monoamine transporter inhibitors and substrates. The study also presents a comparison of hNET models with other related proteins, which could provide new insights into their interaction with therapeutics and aid future development of novel bioactive compounds.

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3

Filošević Vujnović, Ana, Katarina Jović, Emanuel Pištan, and Rozi Andretić Waldowski. "Influence of Dopamine on Fluorescent Advanced Glycation End Products Formation Using Drosophila melanogaster." Biomolecules 11, no. 3 (March 17, 2021): 453. http://dx.doi.org/10.3390/biom11030453.

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Non-enzymatic glycation and covalent modification of proteins leads to Advanced Glycation End products (AGEs). AGEs are biomarkers of aging and neurodegenerative disease, and can be induced by impaired neuronal signaling. The objective of this study was to investigate if manipulation of dopamine (DA) in vitro using the model protein, bovine serum albumin (BSA), and in vivo using the model organism Drosophila melanogaster, influences fluorescent AGEs (fAGEs) formation as an indicator of dopamine-induced oxidation events. DA inhibited fAGEs-BSA synthesis in vitro, suggesting an anti-oxidative effect, which was not observed when flies were fed DA. Feeding flies cocaine and methamphetamine led to increased fAGEs formation. Mutants lacking the dopaminergic transporter or the D1-type showed further elevation of fAGEs accumulation, indicating that the long-term perturbation in DA function leads to higher production of fAGEs. To confirm that DA has oxidative properties in vivo, we fed flies antioxidant quercetin (QUE) together with methamphetamine. QUE significantly decreased methamphetamine-induced fAGEs formation suggesting that the perturbation of DA function in vivo leads to increased oxidation. These findings present arguments for the use of fAGEs as a biomarker of DA-associated neurodegenerative changes and for assessment of antioxidant interventions such as QUE treatment.

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4

Shin, Mimi, and B. Jill Venton. "(Digital Presentation) In Vivo Electrochemical Measurement of Dopamine in Adult Drosophila Mushroom Body." ECS Meeting Abstracts MA2022-01, no. 53 (July 7, 2022): 2197. http://dx.doi.org/10.1149/ma2022-01532197mtgabs.

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Dopamine is a neuromodulator that is secreted to the synapse to relay chemical signals to target neurons. Abnormal levels of dopamine release leads to various neurodegenerative diseases. Therefore, measuring dopamine is essential to understand how dopamine is regulated under normal and pathological conditions. Drosophila melanogaster, the fruit fly, is an ideal model system for studying fundamental neurological processes and diseases because of the availability of sophisticated genetic tools and well conserved neurological processes between mammals and flies. Majority of neuroscience studies involved in modifying a gene and measure the effect of genetic mutation on output behaviors. However, dopamine release is highly dynamic because of the complex activity of dopamine transporters and autoreceptors. Therefore, to understand how dopamine signaling controls the behavior, a direct measurement of changes in dopamine release is necessary. Fast-scan cyclic voltammetry (FSCV) at a carbon-fiber microelectrode is an electrochemical technique that trace concentration changes in dopamine release on the sub-second time scale. Our lab pioneered directly measuring various endogenous neuromodulators in the fly central nervous system with FSCV. Initially, these studies were performed in ex vivo preparations, where brains were isolated from larvae and adult fly, and thus could not monitor neuromodulators during behavior. In this study, we developed in vivo FSCV method to measure phasic dopamine in the mushroom body (MB) during behavior for the first time. The MB in fly has been extensively studied as an associative center for regulating olfactory learning and memory. First, acetylcholine stimulation was applied to the MB heel and medial tip to characterize dopamine signaling and to demonstrate the feasibility of in vivo FSCV in intact fly brain. Application of 0.2 pmol acetylcholine released 0.36 ± 0.06 µM dopamine in the medial tip, which is slightly higher than 0.22 ± 0.06 µM dopamine in the heel. Compartmental differences in evoked release suggest heterogeneity of dopamine regulation in the MB. Nisoxetine, a dopamine transporter inhibitor, and flupentixol, a D2 antagonist, increased stimulated dopamine release. We then applied the in vivo method to monitor changes in behaviorally evoked dopamine release during sugar feeding. Sugar feeding evoked 0.31 ± 0.09 µM dopamine in the medial tip of MB. Flupentixol significantly increased sugar evoked release implying D2 receptor acts as autoreceptor and regulates dopamine signaling during sugar feeding. Therefore, this developed in vivo FSCV method is a great addition to the existing tools to measure endogenous neuromodulators in the fly and valuable for studying real-time dopamine signaling during behavior. This in vivo method also can be further extended to better understand how dopamine and other neuromodulators regulate complex behaviors, such as reward associated learning and memory formation.

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5

Myers, Jennifer L., Maria Porter, Nicholas Narwold, Krishna Bhat, Brigitte Dauwalder, and Gregg Roman. "Mutants of the white ABCG Transporter in Drosophila melanogaster Have Deficient Olfactory Learning and Cholesterol Homeostasis." International Journal of Molecular Sciences 22, no. 23 (November 30, 2021): 12967. http://dx.doi.org/10.3390/ijms222312967.

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Drosophila’s white gene encodes an ATP-binding cassette G-subfamily (ABCG) half-transporter. White is closely related to mammalian ABCG family members that function in cholesterol efflux. Mutants of white have several behavioral phenotypes that are independent of visual defects. This study characterizes a novel defect of white mutants in the acquisition of olfactory memory using the aversive olfactory conditioning paradigm. The w1118 mutants learned slower than wildtype controls, yet with additional training, they reached wildtype levels of performance. The w1118 learning phenotype is also found in the wapricot and wcoral alleles, is dominant, and is rescued by genomic white and mini-white transgenes. Reducing dietary cholesterol strongly impaired olfactory learning for wildtype controls, while w1118 mutants were resistant to this deficit. The w1118 mutants displayed higher levels of cholesterol and cholesterol esters than wildtype under this low-cholesterol diet. Increasing levels of serotonin, dopamine, or both in the white mutants significantly improved w1118 learning. However, serotonin levels were not lower in the heads of the w1118 mutants than in wildtype controls. There were also no significant differences found in synapse numbers within the w1118 brain. We propose that the w1118 learning defect may be due to inefficient biogenic amine signaling brought about by altered cholesterol homeostasis.

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6

Hamilton, P. J., N. G. Campbell, S. Sharma, K. Erreger, F. H. Hansen, C. Saunders, A. N. Belovich, et al. "Drosophila melanogaster: a novel animal model for the behavioral characterization of autism-associated mutations in the dopamine transporter gene." Molecular Psychiatry 18, no. 12 (November 20, 2013): 1235. http://dx.doi.org/10.1038/mp.2013.157.

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7

Makos, Monique A., Kyung-An Han, Michael L. Heien, and Andrew G. Ewing. "Using in Vivo Electrochemistry To Study the Physiological Effects of Cocaine and Other Stimulants on the Drosophila melanogaster Dopamine Transporter." ACS Chemical Neuroscience 1, no. 1 (October 26, 2009): 74–83. http://dx.doi.org/10.1021/cn900017w.

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8

Neckameyer, Wendi S., Stacey Woodrome, Bridgette Holt, and Adam Mayer. "Dopamine and senescence in Drosophila melanogaster☆." Neurobiology of Aging 21, no. 1 (January 2000): 145–52. http://dx.doi.org/10.1016/s0197-4580(99)00109-8.

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9

Giang, Thomas, Steffen Rauchfuss, Maite Ogueta, and Henrike Scholz. "The Serotonin Transporter Expression in Drosophila melanogaster." Journal of Neurogenetics 25, no. 1-2 (February 14, 2011): 17–26. http://dx.doi.org/10.3109/01677063.2011.553002.

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10

Southon, A., A. Farlow, M. Norgate, R. Burke, and J. Camakaris. "Malvolio is a copper transporter in Drosophila melanogaster." Journal of Experimental Biology 211, no. 5 (February 15, 2008): 709–16. http://dx.doi.org/10.1242/jeb.014159.

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11

Vickrey, Trisha L., Ning Xiao, and B. Jill Venton. "Kinetics of the Dopamine Transporter in Drosophila Larva." ACS Chemical Neuroscience 4, no. 5 (April 26, 2013): 832–37. http://dx.doi.org/10.1021/cn400019q.

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12

Andretic, R., and J. Hirsh. "Circadian modulation of dopamine receptor responsiveness in Drosophila melanogaster." Proceedings of the National Academy of Sciences 97, no. 4 (February 15, 2000): 1873–78. http://dx.doi.org/10.1073/pnas.97.4.1873.

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13

Pham, Tuan L. A., Tran Duy Binh, Guanchen Liu, Thanh Q. C. Nguyen, Yen D. H. Nguyen, Ritsuko Sahashi, Tran Thanh Men, and Kaeko Kamei. "Role of Serotonin Transporter in Eye Development of Drosophila melanogaster." International Journal of Molecular Sciences 21, no. 11 (June 8, 2020): 4086. http://dx.doi.org/10.3390/ijms21114086.

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Serotonin transporter (SerT) in the brain is an important neurotransmitter transporter involved in mental health. However, its role in peripheral organs is poorly understood. In this study, we investigated the function of SerT in the development of the compound eye in Drosophila melanogaster. We found that SerT knockdown led to excessive cell death and an increased number of cells in S-phase in the posterior eye imaginal disc. Furthermore, the knockdown of SerT in the eye disc suppressed the activation of Akt, and the introduction of PI3K effectively rescued this phenotype. These results suggested that SerT plays a role in the healthy eye development of D. melanogaster by controlling cell death through the regulation of the PI3K/Akt pathway.

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14

Ueno, Taro, Shoen Kume, and Kazuhiko Kume. "Dopamine controls temperature preferences and energy homeostasis in Drosophila melanogaster." Neuroscience Research 68 (January 2010): e399. http://dx.doi.org/10.1016/j.neures.2010.07.1772.

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15

Martínez-Ramírez, Amparo C., Juan Ferré, and Francisco J. Silva. "Catecholamines in drosophila melanogaster: DOPA and dopamine accumulation during development." Insect Biochemistry and Molecular Biology 22, no. 5 (July 1992): 491–94. http://dx.doi.org/10.1016/0965-1748(92)90145-5.

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16

Ueno, Taro, Jun Tomita, Shoen Kume, and Kazuhiko Kume. "Dopamine Modulates Metabolic Rate and Temperature Sensitivity in Drosophila melanogaster." PLoS ONE 7, no. 2 (February 7, 2012): e31513. http://dx.doi.org/10.1371/journal.pone.0031513.

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17

Fernandez, Robert W., Adesanya A. Akinleye, Marat Nurilov, Omar Feliciano, Matthew Lollar, Rami R. Aijuri, Janis M. O'Donnell, and Anne F. Simon. "Modulation of social space by dopamine in Drosophila melanogaster, but no effect on the avoidance of the Drosophila stress odorant." Biology Letters 13, no. 8 (August 2017): 20170369. http://dx.doi.org/10.1098/rsbl.2017.0369.

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Appropriate response to others is necessary for social interactions. Yet little is known about how neurotransmitters regulate attractive and repulsive social cues. Using genetic and pharmacological manipulations in Drosophila melanogaster , we show that dopamine is contributing the response to others in a social group, specifically, social spacing, but not the avoidance of odours released by stressed flies (dSO). Interestingly, this dopamine-mediated behaviour is prominent only in the day-time, and its effect varies depending on tissue, sex and type of manipulation. Furthermore, alteration of dopamine levels has no effect on dSO avoidance regardless of sex, which suggests that a different neurotransmitter regulates this response.

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18

Chatterjee, Nabanita, Janet Rollina, and Christopher Bazinet. "Testes specific neurotransmitter transporter essential for male fertility in Drosophila melanogaster." Developmental Biology 344, no. 1 (August 2010): 513. http://dx.doi.org/10.1016/j.ydbio.2010.05.361.

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19

MacIver, B., A. McCahill, S. Pathirana, K. Leaper, and M. Bownes. "A putative sodium-dependent inorganic phosphate co-transporter from Drosophila melanogaster." Development Genes and Evolution 210, no. 4 (March 17, 2000): 207–11. http://dx.doi.org/10.1007/s004270050305.

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20

Pyakurel, Poojan, Mimi Shin, and B. Jill Venton. "Nicotinic acetylcholine receptor (nAChR) mediated dopamine release in larval Drosophila melanogaster." Neurochemistry International 114 (March 2018): 33–41. http://dx.doi.org/10.1016/j.neuint.2017.12.012.

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21

SOUTHON, Adam, Richard BURKE, Melanie NORGATE, Philip BATTERHAM, and James CAMAKARIS. "Copper homoeostasis in Drosophila melanogaster S2 cells." Biochemical Journal 383, no. 2 (October 8, 2004): 303–9. http://dx.doi.org/10.1042/bj20040745.

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Copper homoeostasis was investigated in the Drosophila melanogaster S2 cell line to develop an insect model for the study of copper regulation. Real-time PCR studies have demonstrated expression in S2 cells of putative orthologues of human Cu regulatory genes involved in the uptake, transport, sequestration and efflux of Cu. Drosophila orthologues of the mammalian Cu chaperones, ATOX1 (a human orthologue of yeast ATX1), CCS (copper chaperone for superoxide dismutase), COX17 (a human orthologue of yeast COX17), and SCO1 and SCO2, did not significantly respond transcriptionally to increased Cu levels, whereas MtnA, MtnB and MtnD (Drosophila orthologues of human metallothioneins) were up-regulated by Cu in a time- and dose-dependent manner. To examine the effect on Cu homoeostasis, expression of several key copper homoeostasis genes was suppressed using double-stranded RNA interference. Suppression of the MTF-1 (metal-regulatory transcription factor 1), reduced both basal and Cu-induced gene expressions of MtnA, MtnB and MtnD, significantly reducing the tolerance of these cells to increased Cu. Suppression of either Ctr1A (a Drosophila orthologue of yeast CTR1) or Ctr1B significantly reduced Cu uptake from media, demonstrating that both these proteins function to transport Cu into S2 cells. Significantly, Cu induced Ctr1B gene expression, and this could be prevented by suppressing MTF-1, suggesting that Ctr1B might be involved in Cu detoxification. Suppression of DmATP7, the putative homologue of human Cu transporter genes ATP7A and ATP7B, significantly increased Cu accumulation, demonstrating that DmATP7 is essential for efflux of excess Cu. This work is consistent with previous studies in mammalian cells, validating S2 cells as a model system for studying Cu transport and identifying novel Cu regulatory mechanisms.

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22

Pörzgen, Peter, Sang Ki Park, Jay Hirsh, Mark S. Sonders, and Susan G. Amara. "The Antidepressant-Sensitive Dopamine Transporter inDrosophila melanogaster: A Primordial Carrier for Catecholamines." Molecular Pharmacology 59, no. 1 (January 1, 2001): 83–95. http://dx.doi.org/10.1124/mol.59.1.83.

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23

Santoso, Clarissa S., Tracy L. Meehan, Jeanne S. Peterson, Tiara M. Cedano, Christopher V. Turlo, and Kimberly McCall. "The ABC Transporter Eato Promotes Cell Clearance in the Drosophila melanogaster Ovary." G3: Genes|Genomes|Genetics 8, no. 3 (January 2, 2018): 833–43. http://dx.doi.org/10.1534/g3.117.300427.

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24

Jang, Cholsoon, Gina Lee, and Jongkyeong Chung. "LKB1 induces apical trafficking of Silnoon, a monocarboxylate transporter, in Drosophila melanogaster." Journal of Cell Biology 183, no. 1 (October 6, 2008): 11–17. http://dx.doi.org/10.1083/jcb.200807052.

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Silnoon (Sln) is a monocarboxylate transporter (MCT) that mediates active transport of metabolic monocarboxylates such as butyrate and lactate. Here, we identify Sln as a novel LKB1-interacting protein using Drosophila melanogaster genetic modifier screening. Sln expression does not affect cell cycle progression or cell size but specifically enhances LKB1-dependent apoptosis and tissue size reduction. Conversely, down-regulation of Sln suppresses LKB1-dependent apoptosis, implicating Sln as a downstream mediator of LKB1. The kinase activity of LKB1 induces apical trafficking of Sln in polarized cells, and LKB1-dependent Sln trafficking is crucial for triggering apoptosis induced by extracellular butyrate. Given that LKB1 functions to control both epithelial polarity and cell death, we propose Sln is an important downstream target of LKB1.

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25

Neckameyer, Wendi S. "Dopamine and Mushroom Bodies in Drosophila: Experience-Dependent and -Independent Aspects of Sexual Behavior." Learning & Memory 5, no. 1 (May 1, 1998): 157–65. http://dx.doi.org/10.1101/lm.5.1.157.

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Depletion of dopamine in Drosophila melanogaster adult males, accomplished through systemic introduction of the tyrosine hydroxylase inhibitor 3-iodo-tyrosine, severely impaired the ability of these flies to modify their courtship responses to immature males. Mature males, when first exposed to immature males, will perform courtship rituals; the intensity and duration of this behavior rapidly diminshes with time. Dopamine is also required for normal female sexual receptivity; dopamine-depleted females show increased latency to copulation. One kilobase of 5′ upstream information from theDrosophila tyrosine hydroxylase (DTH) gene, when fused to theEscherichia coli β-galactosidase reporter and transduced into the genome of Drosophila melanogaster, is capable of directing expression of the reporter gene in the mushroom bodies, which are believed to mediate learning acquisition and memory retention in flies. Ablation of mushroom bodies by treatment of newly hatched larva with hydroxyurea resulted in the inability of treated mature adult males to cease courtship when placed with untreated immature males. However, functional mushroom bodies were not required for the dopaminergic modulation of an innate behavior, female sexual receptivity. These data suggest that dopamine acts as a signaling molecule within the mushroom bodies to mediate a simple form of learning.

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26

Needham, Andrew J., Monica Kibart, Howard Crossley, Philip W. Ingham, and Simon J. Foster. "Drosophila melanogaster as a model host for Staphylococcus aureus infection." Microbiology 150, no. 7 (July 1, 2004): 2347–55. http://dx.doi.org/10.1099/mic.0.27116-0.

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Staphylococcus aureus is an important pathogen of humans, causing a range of superficial and potentially life-threatening diseases. Infection of the fruit fly Drosophila melanogaster with S. aureus results in systemic infection followed by death. Screening of defined S. aureus mutants for components important in pathogenesis identified perR and pheP, with fly death up to threefold slower after infection with the respective mutants compared to the wild-type. Infection of D. melanogaster with reporter gene fusion strains demonstrated the in vivo expression levels of the accessory gene regulator, agr, α-toxin, hla, and a manganese transporter, mntA. The use of the green fluorescent protein as a reporter under the control of the agr promoter (P3) showed S. aureus microcolony formation in vivo. The disease model also allowed the effect of antibiotic treatment on the flies to be determined. D. melanogaster is a genetically tractable model host for high-throughput analysis of S. aureus virulence determinants.

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27

van der Voet, M., B. Harich, B. Franke, and A. Schenck. "ADHD-associated dopamine transporter, latrophilin and neurofibromin share a dopamine-related locomotor signature in Drosophila." Molecular Psychiatry 21, no. 4 (May 12, 2015): 565–73. http://dx.doi.org/10.1038/mp.2015.55.

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28

CARRILLO, ROLAND, and GREG GIBSON. "Unusual genetic architecture of natural variation affecting drug resistance in Drosophila melanogaster." Genetical Research 80, no. 3 (December 2002): 205–13. http://dx.doi.org/10.1017/s0016672302005888.

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Naturally occurring genetic variation was quantified for survival time of adult Drosophila melanogaster exposed to chronic ingestion of the drugs nicotine, caffeine, dopamine, tyramine and octopamine. Responses to nicotine, tyramine and octopamine were genetically correlated in both sexes, whereas caffeine response correlated with starvation resistance. However, there is also genetic variation that is specific for each of the drugs. Females tended to be more resistant than males to nicotine and caffeine but sex-by-genotype interactions were also seen for these drugs and for the response to dopamine. An unusual and complex genetic architecture was observed in crosses between lines with different responses to caffeine ingestion. Additive and dominance components were clearly seen from the analysis of F1 individuals, but increased female resistance to caffeine in backcross generations and increased male sensitivity in F2 generations confused the interpretation of possible epistatic contributions.

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29

Akiba, Masumi, Kentaro Sugimoto, Risa Aoki, Ryo Murakami, Tomoyuki Miyashita, Riho Hashimoto, Anna Hiranuma, Junji Yamauchi, Taro Ueno, and Takako Morimoto. "Dopamine modulates the optomotor response to unreliable visual stimuli in Drosophila melanogaster." European Journal of Neuroscience 51, no. 3 (February 2020): 822–39. http://dx.doi.org/10.1111/ejn.14648.

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30

Wicker-Thomas, Claude, and Mickael Hamann. "Interaction of dopamine, female pheromones, locomotion and sex behavior in Drosophila melanogaster." Journal of Insect Physiology 54, no. 10-11 (October 2008): 1423–31. http://dx.doi.org/10.1016/j.jinsphys.2008.08.005.

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31

Marican, Charlotte, Line Duportets, Serge Birman, and Jean Marc Jallon. "Female-specific regulation of cuticular hydrocarbon biosynthesis by dopamine in Drosophila melanogaster." Insect Biochemistry and Molecular Biology 34, no. 8 (August 2004): 823–30. http://dx.doi.org/10.1016/j.ibmb.2004.05.002.

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32

Lühn, Kerstin, Anna Laskowska, Jan Pielage, Christian Klämbt, Ute Ipe, Dietmar Vestweber, and Martin K. Wild. "Identification and molecular cloning of a functional GDP-fucose transporter in Drosophila melanogaster." Experimental Cell Research 301, no. 2 (December 2004): 242–50. http://dx.doi.org/10.1016/j.yexcr.2004.08.043.

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33

Vozza, Angelo, Francesco De Leonardis, Eleonora Paradies, Anna De Grassi, Ciro Leonardo Pierri, Giovanni Parisi, Carlo Marya Thomas Marobbio, et al. "Biochemical characterization of a new mitochondrial transporter of dephosphocoenzyme A in Drosophila melanogaster." Biochimica et Biophysica Acta (BBA) - Bioenergetics 1858, no. 2 (February 2017): 137–46. http://dx.doi.org/10.1016/j.bbabio.2016.11.006.

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34

Dhanraj, Vijayraja, Tamilarasan Manivasagam, and Jeyaprakash Karuppaiah. "MYRICETIN ISOLATED FROM TURBINARIA ORNATA AMELIORATES ROTENONE INDUCED PARKINSONISM IN DROSOPHILA MELANOGASTER." International Journal of Pharmacy and Pharmaceutical Sciences 9, no. 10 (November 1, 2017): 39. http://dx.doi.org/10.22159/ijpps.2017v9i11.19931.

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Objective: Parkinson’s disease (PD) is a neurodegenerative disorder which affects the elderly population. Free radicals overproduction, oxidative stress, apoptosis, inflammation and abnormalities in mitochondria are critical mediators of the neuronal degeneration. In the present study neuroprotective activity of myricetin, a flavonoid isolated from brown seaweed Turbinaria ornata have been investigated in rotenone induced experimental PD models of Drosophila melanogaster.Methods: Male fruit flies (Drosophila melanogaster) were fed with an effective dose of 0.1% myricetin three hours before to the treatment with 500 µM of Rotenone (LD 50) for seven days and on 8th day through behavioral analysis the neuroprotective effect of myricetin was investigated for motor coordination in fruit flies. Lipid peroxidation was analyzed by estimating the levels of TBARS. Oxidative stress was determined by estimating the activities of enzymatic antioxidants superoxide dismutase, catalase, and glutathione peroxidase along with the level of reduced glutathione. Dopamine level was estimated in HPLC column detected at 280 nm with UV detectors and degree of apoptosis was studied apoptotic marker Bcl-2, Bax, caspases-3 and 9, cytochrome c and β-actin expressions in the whole body homogenate of fruit flies of experimental groups homogenized in 500μL of 0.1 M phosphate buffers (ice cold, pH, 7.4) containing 1 mmol EDTA.Results: Myricetin maintains the positive behavioral patterns against motor impairments due to the rotenone toxicity, it creates a balance in oxidant and antioxidant status, reduces the oxidative stress and inhibits apoptosis to retard neurodegeneration and maintains the dopamine level with a significant (p<0.05) difference compared to the rotenone treated group.Conclusion: The flavonoid myricetin by reducing the oxidative stress, maintaining the enzymatic antioxidants status and by inhibiting apoptosis prevents the degeneration of dopaminergic neurons. The dopaminergic neurons prevention reduces the depletion of dopamine and thereby promotes the muscular coordination and psychological well being of fruit flies of experimental group. Further in depth molecular level studies are in need to explore the preventive mechanisms of myricetin in Parkinson’s disease.

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35

KUME, Kazuhiko. "A Drosophila dopamine transporter mutant, fumin (fmn), is defective in arousal regulation." Sleep and Biological Rhythms 4, no. 3 (October 2006): 263–73. http://dx.doi.org/10.1111/j.1479-8425.2006.00225.x.

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INOUE, Katsuhisa, You-Jun FEI, Wei HUANG, Lina ZHUANG, Zhong CHEN, and Vadivel GANAPATHY. "Functional identity of Drosophila melanogaster Indy as a cation-independent, electroneutral transporter for tricarboxylic acid-cycle intermediates." Biochemical Journal 367, no. 2 (October 15, 2002): 313–19. http://dx.doi.org/10.1042/bj20021132.

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Indy is a gene in Drosophila melanogaster which, when made dysfunctional, leads to an extension of the average adult life span of the organism. The present study was undertaken to clone the Indy gene-product and to establish its functional identity. We isolated a full-length Indy cDNA from a D. melanogaster cDNA library. The cDNA codes for a protein of 572 amino acids [(Drosophila Indy (drIndy)]. In its amino acid sequence, drIndy exhibits comparable similarity to the two known Na+-coupled dicarboxylate transporters in mammals; namely, NaDC1 (35% identity) and NaDC3 (34% identity). We elucidated the functional characteristics of drIndy in two different heterologous expression systems by using mammalian cells and Xenopus laevis oocytes. These studies show that drIndy is a cation-independent electroneutral transporter for a variety of tricarboxylic acid-cycle intermediates, with preference for citrate compared with succinate. These characteristics of drIndy differ markedly from those of NaDC1 and NaDC3, indicating that neither of these latter transporters is the mammalian functional counterpart of drIndy. Since drIndy is a transporter for tricarboxylic acid-cycle intermediates, dysfunction of the Indy gene may lead to decreased production of metabolic energy in cells, analogous to caloric restriction. This might provide the molecular basis for the observation that disruption of the Indy gene function in Drosophila leads to extension of the average adult life span of the organism.

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Knapp, Elizabeth M., Andrea Kaiser, Rebecca C. Arnold, Maureen M. Sampson, Manuela Ruppert, Li Xu, Matthew I. Anderson, et al. "Mutation of the Drosophila melanogaster serotonin transporter dSERT impacts sleep, courtship, and feeding behaviors." PLOS Genetics 18, no. 11 (November 21, 2022): e1010289. http://dx.doi.org/10.1371/journal.pgen.1010289.

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The Serotonin Transporter (SERT) regulates extracellular serotonin levels and is the target of most current drugs used to treat depression. The mechanisms by which inhibition of SERT activity influences behavior are poorly understood. To address this question in the model organism Drosophila melanogaster, we developed new loss of function mutations in Drosophila SERT (dSERT). Previous studies in both flies and mammals have implicated serotonin as an important neuromodulator of sleep, and our newly generated dSERT mutants show an increase in total sleep and altered sleep architecture that is mimicked by feeding the SSRI citalopram. Differences in daytime versus nighttime sleep architecture as well as genetic rescue experiments unexpectedly suggest that distinct serotonergic circuits may modulate daytime versus nighttime sleep. dSERT mutants also show defects in copulation and food intake, akin to the clinical side effects of SSRIs and consistent with the pleomorphic influence of serotonin on the behavior of D. melanogaster. Starvation did not overcome the sleep drive in the mutants and in male dSERT mutants, the drive to mate also failed to overcome sleep drive. dSERT may be used to further explore the mechanisms by which serotonin regulates sleep and its interplay with other complex behaviors.

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38

Baier, Andrea, Britta Wittek, and Björn Brembs. "Drosophilaas a new model organism for the neurobiology of aggression?" Journal of Experimental Biology 205, no. 9 (May 1, 2002): 1233–40. http://dx.doi.org/10.1242/jeb.205.9.1233.

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SUMMARYWe report here the effects of several neurobiological determinants on aggressive behaviour in the fruitfly Drosophila melanogaster. This study combines behavioural, transgenic, genetic and pharmacological techniques that are well established in the fruitfly, in the novel context of the neurobiology of aggression. We find that octopamine, dopamine and a region in the Drosophila brain called the mushroom bodies, all profoundly influence the expression of aggressive behaviour. Serotonin had no effect. We conclude that Drosophila, with its advanced set of molecular tools and its behavioural richness, has the potential to develop into a new model organism for the study of the neurobiology of aggression.

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39

Braco, Jason T., Jonathan M. Nelson, Cecil J. Saunders, and Erik C. Johnson. "Modulation of Metabolic Hormone Signaling via a Circadian Hormone and Biogenic Amine in Drosophila melanogaster." International Journal of Molecular Sciences 23, no. 8 (April 12, 2022): 4266. http://dx.doi.org/10.3390/ijms23084266.

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In insects, adipokinetic hormone is the primary hormone responsible for the mobilization of stored energy. While a growing body of evidence has solidified the role of adipokinetic hormone (AKH) in modulating the physiological and behavioral responses to metabolic stress, little is known about the upstream endocrine circuit that directly regulates AKH release. We evaluated the AKH-producing cell (APC) transcriptome to identify potential regulatory elements controlling APC activity and found that a number of receptors showed consistent expression levels, including all known dopamine receptors and the pigment dispersing factor receptor (PDFR). We tested the consequences of targeted genetic knockdown and found that APC limited expression of RNAi elements corresponding to each dopamine receptor and caused a significant reduction in survival under starvation. In contrast, PDFR knockdown significantly extended lifespan under starvation, whereas expression of a tethered PDF in APCs resulted in significantly shorter lifespans. These manipulations caused various changes in locomotor activity under starvation. We used live-cell imaging to evaluate the acute effects of the ligands for these receptors on APC activation. Dopamine application led to a transient increase in intracellular calcium in a trehalose-dependent manner. Furthermore, coapplication of dopamine and ecdysone led to a complete loss of this response, suggesting that these two hormones act antagonistically. We also found that PDF application led to an increase in cAMP in APCs and that this response was dependent on expression of the PDFR in APCs. Together, these results suggest a complex circuit in which multiple hormones act on APCs to modulate metabolic state.

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40

Van Swinderen, Bruno, and Rozi Andretic. "Dopamine in Drosophila : setting arousal thresholds in a miniature brain." Proceedings of the Royal Society B: Biological Sciences 278, no. 1707 (January 5, 2011): 906–13. http://dx.doi.org/10.1098/rspb.2010.2564.

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In mammals, the neurotransmitter dopamine (DA) modulates a variety of behaviours, although DA function is mostly associated with motor control and reward. In insects such as the fruitfly, Drosophila melanogaster , DA also modulates a wide array of behaviours, ranging from sleep and locomotion to courtship and learning. How can a single molecule play so many different roles? Adaptive changes within the DA system, anatomical specificity of action and effects on a variety of behaviours highlight the remarkable versatility of this neurotransmitter. Recent genetic and pharmacological manipulations of DA signalling in Drosophila have launched a surfeit of stories—each arguing for modulation of some aspect of the fly's waking (and sleeping) life. Although these stories often seem distinct and unrelated, there are some unifying themes underlying DA function and arousal states in this insect model. One of the central roles played by DA may involve perceptual suppression, a necessary component of both sleep and selective attention.

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White, Daniel, Raquel P. de Sousa Abreu, Andrew Blake, Jeremy Murphy, Shardae Showell, Toshihiro Kitamoto, and Hakeem O. Lawal. "Deficits in the vesicular acetylcholine transporter alter lifespan and behavior in adult Drosophila melanogaster." Neurochemistry International 137 (July 2020): 104744. http://dx.doi.org/10.1016/j.neuint.2020.104744.

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42

Roman, Gregg, Victoria Meller, Kwok Hang Wu, and Ronald L. Davis. "The opt1 gene ofDrosophila melanogaster encodes a proton-dependent dipeptide transporter." American Journal of Physiology-Cell Physiology 275, no. 3 (September 1, 1998): C857—C869. http://dx.doi.org/10.1152/ajpcell.1998.275.3.c857.

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We have cloned and characterized the opt1 gene of Drosophila melanogaster. This gene encodes a protein with significant similarity to the PTR family of oligopeptide transporters. The OPT1 protein is localized to the apical epithelial membrane domains of the midgut, rectum, and female reproductive tract. The opt1 message is maternally loaded into developing oocytes, and OPT1 is found in the α-yolk spheres of the developing embryo. It is also found throughout the neuropil of the central nervous system, with elevated expression within the α- and β-lobes of the mushroom bodies. Transport activity was examined in HeLa cells transiently expressing OPT1. This protein is a high-affinity transporter of alanylalanine; the approximate K mconstant is 48.8 μM for this substrate. OPT1 dipeptide transport activity is proton dependent. The ability of selected β-lactams to inhibit alanylalanine transport suggests that OPT1 has a broad specificity in amino acid side chains and has a substrate requirement for an α-amino group. Together these data suggest an important role for OPT1 in regulating amino acid availability.

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43

Penmatsa, Aravind, Kevin H. Wang, and Eric Gouaux. "X-ray structures of Drosophila dopamine transporter in complex with nisoxetine and reboxetine." Nature Structural & Molecular Biology 22, no. 6 (May 11, 2015): 506–8. http://dx.doi.org/10.1038/nsmb.3029.

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44

Jakšić, Ana Marija, Julia Karner, Viola Nolte, Sheng-Kai Hsu, Neda Barghi, François Mallard, Kathrin Anna Otte, Lidija Svečnjak, Kirsten-André Senti, and Christian Schlötterer. "Neuronal Function and Dopamine Signaling Evolve at High Temperature in Drosophila." Molecular Biology and Evolution 37, no. 9 (May 13, 2020): 2630–40. http://dx.doi.org/10.1093/molbev/msaa116.

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Abstract Neuronal activity is temperature sensitive and affects behavioral traits important for individual fitness, such as locomotion and courtship. Yet, we do not know enough about the evolutionary response of neuronal phenotypes in new temperature environments. Here, we use long-term experimental evolution of Drosophila simulans populations exposed to novel temperature regimes. Here, we demonstrate a direct relationship between thermal selective pressure and the evolution of neuronally expressed molecular and behavioral phenotypes. Several essential neuronal genes evolve lower expression at high temperatures and higher expression at low temperatures, with dopaminergic neurons standing out by displaying the most consistent expression change across independent replicates. We functionally validate the link between evolved gene expression and behavioral changes by pharmacological intervention in the experimentally evolved D. simulans populations as well as by genetically triggered expression changes of key genes in D. melanogaster. As natural temperature clines confirm our results for Drosophila and Anopheles populations, we conclude that neuronal dopamine evolution is a key factor for temperature adaptation.

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45

Budnik, Vivian, and Kalpana White. "Genetic dissection of dopamine and serotonin synthesis in the nervous system of Drosophila melanogaster." Journal of Neurogenetics 4, no. 1 (January 1987): 309–14. http://dx.doi.org/10.3109/01677068709102351.

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46

Rauschenbach, I. Yu, E. K. Karpova, A. A. Alekseev, N. V. Adonyeva, L. V. Shumnaya, and N. E. Gruntenko. "Interplay of insulin and dopamine signaling pathways in the control of Drosophila melanogaster fitness." Doklady Biochemistry and Biophysics 461, no. 1 (March 2015): 135–38. http://dx.doi.org/10.1134/s1607672915020179.

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47

Izoré, Thierry, Julien Tailhades, Mathias Henning Hansen, Joe A. Kaczmarski, Colin J. Jackson, and Max J. Cryle. "Drosophila melanogaster nonribosomal peptide synthetase Ebony encodes an atypical condensation domain." Proceedings of the National Academy of Sciences 116, no. 8 (January 31, 2019): 2913–18. http://dx.doi.org/10.1073/pnas.1811194116.

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The protein Ebony from Drosophila melanogaster plays a central role in the regulation of histamine and dopamine in various tissues through condensation of these amines with β-alanine. Ebony is a rare example of a nonribosomal peptide synthetase (NRPS) from a higher eukaryote and contains a C-terminal sequence that does not correspond to any previously characterized NRPS domain. We have structurally characterized this C-terminal domain and have discovered that it adopts the aryl-alkylamine-N-acetyl transferase (AANAT) fold, which is unprecedented in NRPS biology. Through analysis of ligand-bound structures, activity assays, and binding measurements, we have determined how this atypical condensation domain is able to provide selectivity for both the carrier protein-bound amino acid and the amine substrates, a situation that remains unclear for standard condensation domains identified to date from NRPS assembly lines. These results demonstrate that the C terminus of Ebony encodes a eukaryotic example of an alternative type of NRPS condensation domain; they also illustrate how the catalytic components of such assembly lines are significantly more diverse than a minimal set of conserved functional domains.

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48

Demchyshyn, L. L., Z. B. Pristupa, K. S. Sugamori, E. L. Barker, R. D. Blakely, W. J. Wolfgang, M. A. Forte, and H. B. Niznik. "Cloning, expression, and localization of a chloride-facilitated, cocaine-sensitive serotonin transporter from Drosophila melanogaster." Proceedings of the National Academy of Sciences 91, no. 11 (May 24, 1994): 5158–62. http://dx.doi.org/10.1073/pnas.91.11.5158.

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49

Zhang, Jiajun, Lucie Lentz, Jens Goldammer, Jessica Iliescu, Jun Tanimura, and Thomas Dieter Riemensperger. "Asymmetric Presynaptic Depletion of Dopamine Neurons in a Drosophila Model of Parkinson’s Disease." International Journal of Molecular Sciences 24, no. 10 (May 11, 2023): 8585. http://dx.doi.org/10.3390/ijms24108585.

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Parkinson’s disease (PD) often displays a strong unilateral predominance in arising symptoms. PD is correlated with dopamine neuron (DAN) degeneration in the substantia nigra pars compacta (SNPC), and in many patients, DANs appear to be affected more severely on one hemisphere than the other. The reason for this asymmetric onset is far from being understood. Drosophila melanogaster has proven its merit to model molecular and cellular aspects of the development of PD. However, the cellular hallmark of the asymmetric degeneration of DANs in PD has not yet been described in Drosophila. We ectopically express human α-synuclein (hα-syn) together with presynaptically targeted syt::HA in single DANs that innervate the Antler (ATL), a symmetric neuropil located in the dorsomedial protocerebrum. We find that expression of hα-syn in DANs innervating the ATL yields asymmetric depletion of synaptic connectivity. Our study represents the first example of unilateral predominance in an invertebrate model of PD and will pave the way to the investigation of unilateral predominance in the development of neurodegenerative diseases in the genetically versatile invertebrate model Drosophila.

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50

Szöllősi, Daniel. "The disease-causing mutation G108Q destabilizes the Drosophila dopamine transporter in molecular dynamic simulations." Intrinsic Activity 4, Suppl. 2 (August 29, 2016): A18.26. http://dx.doi.org/10.25006/ia.4.s2-a18.26.

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