vesicular inhibitory amino acid transport proteins


Summary: A family of vesicular neurotransmitter transporter proteins that sequester the inhibitory neurotransmitters GLYCINE; GAMMA-AMINOBUTYRIC ACID; and possibly GAMMA-HYDROXYBUTYRATE into SECRETORY VESICLES.

Top Publications

  1. Zhao S, Ting J, Atallah H, Qiu L, Tan J, Gloss B, et al. Cell type–specific channelrhodopsin-2 transgenic mice for optogenetic dissection of neural circuitry function. Nat Methods. 2011;8:745-52 pubmed
    ..This resource of cell type–specific ChR2(H134R) mouse lines will facilitate the precise mapping of neuronal connectivity and the dissection of the neural basis of behavior. ..
  2. Juge N, Muroyama A, Hiasa M, Omote H, Moriyama Y. Vesicular inhibitory amino acid transporter is a Cl-/gamma-aminobutyrate Co-transporter. J Biol Chem. 2009;284:35073-8 pubmed publisher
    ..It is concluded that Cl(-) plays an essential role in vesicular storage of GABA and glycine. ..
  3. Vetrivelan R, Fuller P, Tong Q, Lu J. Medullary circuitry regulating rapid eye movement sleep and motor atonia. J Neurosci. 2009;29:9361-9 pubmed publisher
    ..These findings, together, demonstrate that SOM glutamatergic neurons comprise key elements of the medullary circuitry mediating REM atonia. ..
  4. Guo C, Stella S, Hirano A, Brecha N. Plasmalemmal and vesicular gamma-aminobutyric acid transporter expression in the developing mouse retina. J Comp Neurol. 2009;512:6-26 pubmed publisher
    ..These findings demonstrate that GABA uptake and release are initially established in the inner retina during the first postnatal week and that these systems subsequently mature in the outer retina during the second postnatal week. ..
  5. Sagne C, El Mestikawy S, Isambert M, Hamon M, Henry J, Giros B, et al. Cloning of a functional vesicular GABA and glycine transporter by screening of genome databases. FEBS Lett. 1997;417:177-83 pubmed
    ..These observations, consistent with previous data on GABA and glycine uptake by synaptic vesicles, demonstrate that the mouse clone encodes a vesicular inhibitory amino acid transporter. ..
  6. Polgár E, Sardella T, Watanabe M, Todd A. Quantitative study of NPY-expressing GABAergic neurons and axons in rat spinal dorsal horn. J Comp Neurol. 2011;519:1007-23 pubmed publisher
    ..These results show that NPY-containing neurons make up a considerable proportion of the inhibitory interneurons in laminae I-III, and that their axons preferentially target certain classes of dorsal horn neuron. ..
  7. Yasaka T, Tiong S, Hughes D, Riddell J, Todd A. Populations of inhibitory and excitatory interneurons in lamina II of the adult rat spinal dorsal horn revealed by a combined electrophysiological and anatomical approach. Pain. 2010;151:475-88 pubmed publisher
    ..Combining this approach with identification of other neurochemical markers should allow further clarification of neuronal circuitry in the superficial dorsal horn. ..
  8. Jedlicka P, Hoon M, Papadopoulos T, Vlachos A, Winkels R, Poulopoulos A, et al. Increased dentate gyrus excitability in neuroligin-2-deficient mice in vivo. Cereb Cortex. 2011;21:357-67 pubmed publisher
    ..Collectively, our data demonstrate for the first time that deletion of NL2 increases excitability of cortical neurons in the hippocampus of intact animals, most likely through impaired GABA(A)R clustering. ..
  9. Tong Q, Ye C, Jones J, Elmquist J, Lowell B. Synaptic release of GABA by AgRP neurons is required for normal regulation of energy balance. Nat Neurosci. 2008;11:998-1000 pubmed publisher
    ..These mice are lean, resistant to obesity and have an attenuated hyperphagic response to ghrelin. Thus, GABA release from AgRP neurons is important in regulating energy balance. ..

More Information


  1. Polgár E, Todd A. Tactile allodynia can occur in the spared nerve injury model in the rat without selective loss of GABA or GABA(A) receptors from synapses in laminae I-II of the ipsilateral spinal dorsal horn. Neuroscience. 2008;156:193-202 pubmed publisher
    ..An alternative explanation for disinhibition after nerve injury is that it results from reduced excitatory drive to GABAergic dorsal horn neurons following loss of primary afferent input to these cells. ..
  2. Neal Perry G, Zeevalk G, Shu J, Etgen A. Restoration of the luteinizing hormone surge in middle-aged female rats by altering the balance of GABA and glutamate transmission in the medial preoptic area. Biol Reprod. 2008;79:878-88 pubmed publisher
  3. Tabuchi K, Blundell J, Etherton M, Hammer R, Liu X, Powell C, et al. A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice. Science. 2007;318:71-6 pubmed
    ..These data suggest that increased inhibitory synaptic transmission may contribute to human ASDs and that the R451C knockin mice may be a useful model for studying autism-related behaviors. ..
  4. Aubrey K, Rossi F, Ruivo R, Alboni S, Bellenchi G, Le Goff A, et al. The transporters GlyT2 and VIAAT cooperate to determine the vesicular glycinergic phenotype. J Neurosci. 2007;27:6273-81 pubmed
    ..Together, these results suggest that an increased cytosolic availability of glycine in VIAAT-containing terminals was crucial for the emergence of glycinergic transmission in vertebrates. ..
  5. Fujii M, Arata A, Kanbara Kume N, Saito K, Yanagawa Y, Obata K. Respiratory activity in brainstem of fetal mice lacking glutamate decarboxylase 65/67 and vesicular GABA transporter. Neuroscience. 2007;146:1044-52 pubmed
    ..These results indicate that the lack of GABA and glycine impairs the function of the respiratory network in mouse fetuses and the impairment progresses with fetal age. ..
  6. Jiang M, Swann J. A role for L-type calcium channels in the maturation of parvalbumin-containing hippocampal interneurons. Neuroscience. 2005;135:839-50 pubmed
    ..2 and especially voltage-gated calcium channel subunit 1.3 and that these channels likely regulate the development of these interneurons in an activity-dependent manner. ..
  7. Chih B, Engelman H, Scheiffele P. Control of excitatory and inhibitory synapse formation by neuroligins. Science. 2005;307:1324-8 pubmed
    ..Electrophysiological analysis revealed a predominant reduction of inhibitory synaptic function. Thus, neuroligins control the formation and functional balance of excitatory and inhibitory synapses in hippocampal neurons. ..
  8. Danglot L, Rostaing P, Triller A, Bessis A. Morphologically identified glycinergic synapses in the hippocampus. Mol Cell Neurosci. 2004;27:394-403 pubmed
    ..Finally, GlyR clusters could be detected at synaptic sites with the GABAA receptor gamma2 subunit and gephyrin, suggesting that mixed GABA/glycine synapses might exist in the hippocampus. ..
  9. Ottem E, Godwin J, Krishnan S, Petersen S. Dual-phenotype GABA/glutamate neurons in adult preoptic area: sexual dimorphism and function. J Neurosci. 2004;24:8097-105 pubmed
    ..Thus, we propose a new model for ovulation that includes dual-phenotype GABA/glutamate neurons as central transducers of hormonal and neural signals to GnRH neurons. ..
  10. McIntire S, Reimer R, Schuske K, Edwards R, Jorgensen E. Identification and characterization of the vesicular GABA transporter. Nature. 1997;389:870-6 pubmed
    ..Thus VGAT is the first of a new family of neurotransmitter transporters. ..
  11. Wojcik S, Katsurabayashi S, Guillemin I, Friauf E, Rosenmund C, Brose N, et al. A shared vesicular carrier allows synaptic corelease of GABA and glycine. Neuron. 2006;50:575-87 pubmed
    ..Since GABA and glycine compete for vesicular uptake, these data point to a close association of Viaat with GABA-synthesizing enzymes as a key factor in specifying GABAergic neuronal phenotypes. ..
  12. Wang Y, Kakizaki T, Sakagami H, Saito K, Ebihara S, Kato M, et al. Fluorescent labeling of both GABAergic and glycinergic neurons in vesicular GABA transporter (VGAT)-venus transgenic mouse. Neuroscience. 2009;164:1031-43 pubmed publisher
    ..These results demonstrate that the VGAT-Venus line #39 mouse should be useful for studies on function and morphology of inhibitory neurons in the CNS. ..
  13. Woo J, Kwon S, Choi S, Kim S, Lee J, Dunah A, et al. Trans-synaptic adhesion between NGL-3 and LAR regulates the formation of excitatory synapses. Nat Neurosci. 2009;12:428-37 pubmed publisher
    ..Competitive inhibition by soluble LAR reduced NGL-3-induced presynaptic differentiation. These results suggest that the trans-synaptic adhesion between NGL-3 and LAR regulates excitatory synapse formation in a bidirectional manner. ..
  14. Yoshida R, Sakurai D, Horie T, Kawakami I, Tsuda M, Kusakabe T. Identification of neuron-specific promoters in Ciona intestinalis. Genesis. 2004;39:130-40 pubmed
    ..These promoters can be a powerful tool for studying molecular mechanisms of neuronal development as well as neuron networks and functions in ascidians. ..
  15. Heine S, Michalakis S, Kallenborn Gerhardt W, Lu R, Lim H, Weiland J, et al. CNGA3: a target of spinal nitric oxide/cGMP signaling and modulator of inflammatory pain hypersensitivity. J Neurosci. 2011;31:11184-92 pubmed publisher
    ..Our results provide evidence that CNGA3 contributes in an inhibitory manner to the central sensitization of pain pathways during inflammatory pain as a target of NO/cGMP signaling. ..
  16. Kuriu T, Yanagawa Y, Konishi S. Activity-dependent coordinated mobility of hippocampal inhibitory synapses visualized with presynaptic and postsynaptic tagged-molecular markers. Mol Cell Neurosci. 2012;49:184-95 pubmed publisher
    ..Such a neural activity-dependent dynamic change in GABAergic synaptic morphology is likely to play a critical role in the regulatory mechanism underlying the formation and plasticity of inhibitory synapses. ..
  17. Fan K, Baufreton J, Surmeier D, Chan C, Bevan M. Proliferation of external globus pallidus-subthalamic nucleus synapses following degeneration of midbrain dopamine neurons. J Neurosci. 2012;32:13718-28 pubmed publisher
    ..This adaptation may oppose hyperactivity but could also contribute to abnormal firing patterns in the parkinsonian STN. ..
  18. Bouvier D, Tremblay M, Riad M, Corera A, Gingras D, Horn K, et al. EphA4 is localized in clathrin-coated and synaptic vesicles in adult mouse brain. J Neurochem. 2010;113:153-65 pubmed publisher
    ..This trafficking itinerary may serve to regulate the levels of EphA4 in the synaptic plasma membrane and thereby modulate signaling events that contribute to synaptic plasticity. ..
  19. Dimitrov E, Yanagawa Y, Usdin T. Forebrain GABAergic projections to locus coeruleus in mouse. J Comp Neurol. 2013;521:2373-97 pubmed publisher
    ..This description of GABAergic projections from the CAmy and PLH to the LC clarifies important forebrain sources of inhibitory control of central nervous system noradrenergic activity. ..
  20. Teng L, Tang Y, Sun F, An S, Zhang C, Yang X, et al. Non-neuronal release of gamma-aminobutyric Acid by embryonic pluripotent stem cells. Stem Cells Dev. 2013;22:2944-53 pubmed publisher
    ..We found that embryonic PS cells processed a GABAergic circuit machinery and spontaneously released GABA, which suggests the potential that embryonic PS cells could autonomously establish a GABA niche via release of the transmitter. ..
  21. Ferraguti F, Klausberger T, Cobden P, Baude A, Roberts J, Szucs P, et al. Metabotropic glutamate receptor 8-expressing nerve terminals target subsets of GABAergic neurons in the hippocampus. J Neurosci. 2005;25:10520-36 pubmed
  22. Boulland J, Jenstad M, Boekel A, Wouterlood F, Edwards R, Storm Mathisen J, et al. Vesicular glutamate and GABA transporters sort to distinct sets of vesicles in a population of presynaptic terminals. Cereb Cortex. 2009;19:241-8 pubmed publisher
    ..Our data reconcile previous apparently conflicting reports on the physiology of the dentate afferents from SuM and demonstrate that both glutamate and GABA may be released from a single nerve terminal. ..
  23. Fung S, Sivagnanasundaram S, Weickert C. Lack of change in markers of presynaptic terminal abundance alongside subtle reductions in markers of presynaptic terminal plasticity in prefrontal cortex of schizophrenia patients. Biol Psychiatry. 2011;69:71-9 pubmed publisher
    ..A reduction in the plasticity of synaptic terminals supports the hypothesis that their reduced modifiability may contribute to neuropathology and working memory deficits in schizophrenia. ..
  24. Levav Rabkin T, Melamed O, Clarke G, Farber M, Cryan J, Dinan T, et al. A sensitive period of mice inhibitory system to neonatal GABA enhancement by vigabatrin is brain region dependent. Neuropsychopharmacology. 2010;35:1138-54 pubmed publisher
    ..These findings provide novel insights into the deleterious consequences observed in children following prenatal and neonatal exposure to GABA-potentiating drugs. ..
  25. Zhang Z, Zak J, Liu H. MeCP2 is required for normal development of GABAergic circuits in the thalamus. J Neurophysiol. 2010;103:2470-81 pubmed publisher
    ..Our findings suggest that MeCP2 differentially regulates the development of GABAergic synapses in excitatory and inhibitory neurons in the thalamus...
  26. Gómez Lira G, Lamas M, Romo Parra H, Gutierrez R. Programmed and induced phenotype of the hippocampal granule cells. J Neurosci. 2005;25:6939-46 pubmed
  27. Hayashi M, Otsuka M, Morimoto R, Muroyama A, Uehara S, Yamamoto A, et al. Vesicular inhibitory amino acid transporter is present in glucagon-containing secretory granules in alphaTC6 cells, mouse clonal alpha-cells, and alpha-cells of islets of Langerhans. Diabetes. 2003;52:2066-74 pubmed
    ..the present results suggest more complex features of the GABAergic phenotype of islets than previously supposed. ..
  28. Pillai A, Mansouri A, Behringer R, Westphal H, Goulding M. Lhx1 and Lhx5 maintain the inhibitory-neurotransmitter status of interneurons in the dorsal spinal cord. Development. 2007;134:357-66 pubmed
    ..Lhx1 and Lhx5 therefore function together with Pax2, Pax5 and Pax8 to establish a GABAergic inhibitory-neurotransmitter program in dorsal horn interneurons. ..
  29. Krenzer M, Anaclet C, Vetrivelan R, Wang N, Vong L, Lowell B, et al. Brainstem and spinal cord circuitry regulating REM sleep and muscle atonia. PLoS ONE. 2011;6:e24998 pubmed publisher
    ..These findings reveal the critical and divergent in vivo role of pontine glutamate and spinal cord GABA/glycine in the regulation of REM sleep and atonia and suggest a possible etiological basis for REM sleep behavior disorder (RBD). ..
  30. Dejanovic B, Schwarz G. Neuronal nitric oxide synthase-dependent S-nitrosylation of gephyrin regulates gephyrin clustering at GABAergic synapses. J Neurosci. 2014;34:7763-8 pubmed publisher
    ..In conclusion, S-nitrosylation of gephyrin is important for homeostatic assembly and plasticity of GABAergic synapses. ..
  31. Hassani O, Henny P, Lee M, Jones B. GABAergic neurons intermingled with orexin and MCH neurons in the lateral hypothalamus discharge maximally during sleep. Eur J Neurosci. 2010;32:448-57 pubmed publisher
    ..They could accordingly dampen arousal with muscle tone and promote sleep, including PS with muscle atonia. ..
  32. Eleore L, Ardehali M, Vassias I, Vidal P, de Waele C. Amino acid transporter (VIAAT, VGLUT2) and chloride cotransporter (KCC1, KCC2 and NKCC1) expression in the vestibular nuclei of intact and labyrinthectomized rat. Exp Brain Res. 2007;182:449-58 pubmed
  33. Wester M, Teasley D, Byers S, Saha M. Expression patterns of glycine transporters (xGlyT1, xGlyT2, and xVIAAT) in Xenopus laevis during early development. Gene Expr Patterns. 2008;8:261-70 pubmed publisher
  34. Gallus L, Ferrando S, Gambardella C, Diaspro A, Bianchini P, Piazza V, et al. The GABAergic-like system in the cyprid of Balanus amphitrite (=Amphibalanus amphitrite) (Cirripedia, Crustacea). Biofouling. 2010;26:155-65 pubmed publisher
    ..These results suggest a neurotransmitter/neuromodulatory role for GABA in thoracic muscle contraction and regulatory functions in compound eyes and antennules of B. amphitrite cyprids. ..
  35. Belichenko P, Kleschevnikov A, Masliah E, Wu C, Takimoto Kimura R, Salehi A, et al. Excitatory-inhibitory relationship in the fascia dentata in the Ts65Dn mouse model of Down syndrome. J Comp Neurol. 2009;512:453-66 pubmed publisher
    ..The results demonstrate a significant alteration of inhibitory synapses in the fascia dentata of Ts65Dn mice. ..
  36. Xiang C, Zhang K, Johnson R, Jacquin M, Chen Z. The transcription factor, Lmx1b, promotes a neuronal glutamate phenotype and suppresses a GABA one in the embryonic trigeminal brainstem complex. Somatosens Mot Res. 2012;29:1-12 pubmed publisher
  37. Imbrosci B, Neubacher U, White R, Eysel U, Mittmann T. Shift from phasic to tonic GABAergic transmission following laser-lesions in the rat visual cortex. Pflugers Arch. 2013;465:879-93 pubmed publisher
    ..We therefore suggest that it is not, as traditionally assumed, the overall inhibitory strength to be primarily compromised by a cortical lesion but rather the temporal accuracy of the GABAergic synaptic signaling. ..
  38. Khan M, De Sevilla L, Mahesh V, Brann D. Enhanced glutamatergic and decreased GABAergic synaptic appositions to GnRH neurons on proestrus in the rat: modulatory effect of aging. PLoS ONE. 2010;5:e10172 pubmed publisher
  39. Tarabal O, Caraballo Miralles V, Cardona Rossinyol A, Correa F, Olmos G, Llado J, et al. Mechanisms involved in spinal cord central synapse loss in a mouse model of spinal muscular atrophy. J Neuropathol Exp Neurol. 2014;73:519-35 pubmed publisher
    ..Together, our observations suggest that the earliest change occurring in SMN?7 mice is the loss of excitatory glutamatergic synaptic inputs to MNs; reduced excitability may enhance their vulnerability to degeneration and death. ..
  40. Singer B, GAMELLI A, Fuller C, Temme S, Parent J, Murphy G. Compensatory network changes in the dentate gyrus restore long-term potentiation following ablation of neurogenesis in young-adult mice. Proc Natl Acad Sci U S A. 2011;108:5437-42 pubmed publisher
    ..These findings suggest that prolonged suppression of neurogenesis in young-adult mice results in wide-ranging compensatory changes in the structure and dynamics of the dentate gyrus that function to restore plasticity. ..
  41. Eastman C, Horvitz H, Jin Y. Coordinated transcriptional regulation of the unc-25 glutamic acid decarboxylase and the unc-47 GABA vesicular transporter by the Caenorhabditis elegans UNC-30 homeodomain protein. J Neurosci. 1999;19:6225-34 pubmed
    ..Our data establish a mechanism for cell type-specific transcriptional coregulation of genes required for the synthesis and packaging of the neurotransmitter GABA. ..
  42. Harada K, Matsuoka H, Nakamura J, Fukuda M, Inoue M. Storage of GABA in chromaffin granules and not in synaptic-like microvesicles in rat adrenal medullary cells. J Neurochem. 2010;114:617-26 pubmed publisher
    ..We conclude that GABA is stored in chromaffin granules in rat and bovine AM cells through VGAT...
  43. Cheng L, Arata A, Mizuguchi R, Qian Y, Karunaratne A, Gray P, et al. Tlx3 and Tlx1 are post-mitotic selector genes determining glutamatergic over GABAergic cell fates. Nat Neurosci. 2004;7:510-7 pubmed
    ..Finally, excess GABA-mediated inhibition caused dysfunction of central respiratory circuits in Tlx3 mutant mice. ..
  44. Wierenga C, Becker N, Bonhoeffer T. GABAergic synapses are formed without the involvement of dendritic protrusions. Nat Neurosci. 2008;11:1044-52 pubmed publisher
    ..These findings imply that fundamentally different mechanisms underlie the generation of GABAergic and glutamatergic synapses. ..
  45. Darna M, Schmutz I, Richter K, Yelamanchili S, Pendyala G, Höltje M, et al. Time of day-dependent sorting of the vesicular glutamate transporter to the plasma membrane. J Biol Chem. 2009;284:4300-7 pubmed publisher
    ..We conclude that VGLUTs are sorted diurnally to the plasma membrane to modulate glutamate transmission during a day/night cycle, whereas VGAT expression is not oscillating but is increased in the presence of a light/dark cycle. ..
  46. Oh W, Noggle S, Maddox D, Condie B. The mouse vesicular inhibitory amino acid transporter gene: expression during embryogenesis, analysis of its core promoter in neural stem cells and a reconsideration of its alternate splicing. Gene. 2005;351:39-49 pubmed
    ..Brain Res. Mol Brain Res. 110 (2003), 126-139]. Instead, the alternative isoform Viaat-a appears to be due to PCR artifacts that have occurred independently in multiple labs. ..
  47. Bragina L, Melone M, Fattorini G, Conti F. Clozapine upregulates the expression of the vesicular GABA transporter (VGAT) in rat frontal cortex. Mol Psychiatry. 2007;12:612-3 pubmed
  48. Eto K, Wake H, Watanabe M, Ishibashi H, Noda M, Yanagawa Y, et al. Inter-regional contribution of enhanced activity of the primary somatosensory cortex to the anterior cingulate cortex accelerates chronic pain behavior. J Neurosci. 2011;31:7631-6 pubmed publisher
    ..The present results will provide development of efficient therapeutic strategies against chronic pain by focusing on the S1 and ACC. ..
  49. Jellali A, Stussi Garaud C, Gasnier B, Rendon A, Sahel J, Dreyfus H, et al. Cellular localization of the vesicular inhibitory amino acid transporter in the mouse and human retina. J Comp Neurol. 2002;449:76-87 pubmed
    ..VIAAT localization in mouse and human horizontal cells further support the role of inhibitory transmitters in lateral inhibition at the photoreceptor terminals. ..
  50. Raghu S, Claussen J, Borst A. Neurons with GABAergic phenotype in the visual system of Drosophila. J Comp Neurol. 2013;521:252-65 pubmed publisher
    ..This detailed map of neurons with GABAergic phenotype will contribute to the future neurogenetic dissection of information processing circuits in the fly visual system. ..
  51. Zhou F, Roper S. Densities of glutamatergic and GABAergic presynaptic terminals are altered in experimental cortical dysplasia. Epilepsia. 2010;51:1468-76 pubmed publisher
    ..We analyzed the number of excitatory and inhibitory presynaptic terminals in the neocortex of irradiated rats to better characterize altered connectivity in experimental CD...
  52. Herde M, Iremonger K, Constantin S, Herbison A. GnRH neurons elaborate a long-range projection with shared axonal and dendritic functions. J Neurosci. 2013;33:12689-97 pubmed publisher
    ..This structure, termed a "dendron," greatly expands the dynamic control of GnRH secretion into the pituitary portal system to regulate fertility. ..
  53. Barnstedt O, Owald D, Felsenberg J, Brain R, Moszynski J, Talbot C, et al. Memory-Relevant Mushroom Body Output Synapses Are Cholinergic. Neuron. 2016;89:1237-1247 pubmed publisher
    ..Therefore, olfactory memories in Drosophila are likely stored as plasticity of cholinergic synapses. ..