vesicular glutamate transport proteins


Summary: A family of vesicular neurotransmitter transporter proteins that were originally characterized as sodium dependent inorganic phosphate cotransporters. Vesicular glutamate transport proteins sequester the excitatory neurotransmitter GLUTAMATE from the CYTOPLASM into SECRETORY VESICLES in exchange for lumenal PROTONS.

Top Publications

  1. Weston M, Nehring R, Wojcik S, Rosenmund C. Interplay between VGLUT isoforms and endophilin A1 regulates neurotransmitter release and short-term plasticity. Neuron. 2011;69:1147-59 pubmed publisher
  2. Daniels R, Gelfand M, Collins C, DiAntonio A. Visualizing glutamatergic cell bodies and synapses in Drosophila larval and adult CNS. J Comp Neurol. 2008;508:131-52 pubmed publisher
    ..This description of the glutamatergic system in Drosophila highlights the prevalence of glutamatergic neurons in the CNS and presents tools for future study and manipulation of glutamatergic transmission. ..
  3. Horie T, Kusakabe T, Tsuda M. Glutamatergic networks in the Ciona intestinalis larva. J Comp Neurol. 2008;508:249-63 pubmed publisher
    ..Our results suggest that glutamatergic neurotransmission plays a major role in sensory systems and in the integration of the sensory inputs of the ascidian larva. ..
  4. Wu X, Xue L, Mohan R, Paradiso K, Gillis K, Wu L. The origin of quantal size variation: vesicular glutamate concentration plays a significant role. J Neurosci. 2007;27:3046-56 pubmed
    ..In summary, the different amplitudes of mEPSCs were mainly attributable to release of vesicles having similar volumes, but different glutamate amounts, suggesting that [Glu]v is a main source of quantal size variation. ..
  5. Nickerson Poulin A, Guerci A, El Mestikawy S, Semba K. Vesicular glutamate transporter 3 immunoreactivity is present in cholinergic basal forebrain neurons projecting to the basolateral amygdala in rat. J Comp Neurol. 2006;498:690-711 pubmed
    ..These findings indicate that BF cholinergic neurons containing VGLUT3 project to the basolateral amygdala and suggest that these neurons might have the capacity to release both acetylcholine and glutamate. ..
  6. Matsuo R, Kobayashi S, Watanabe S, Namiki S, Iinuma S, Sakamoto H, et al. Glutamatergic neurotransmission in the procerebrum (olfactory center) of a terrestrial mollusk. J Neurosci Res. 2009;87:3011-23 pubmed publisher
    ..Our observations suggest strongly that the oscillation of the local field potential is driven by the glutamate released by bursting neurons in the procerebrum. ..
  7. Zander J, Münster Wandowski A, Brunk I, Pahner I, Gómez Lira G, Heinemann U, et al. Synaptic and vesicular coexistence of VGLUT and VGAT in selected excitatory and inhibitory synapses. J Neurosci. 2010;30:7634-45 pubmed publisher
    ..Thus, synaptic and vesicular coexistence of VGLUT and VGAT is more widespread than previously anticipated, putatively influencing fine-tuning and control of synaptic plasticity. ..
  8. Gillespie D, Kim G, Kandler K. Inhibitory synapses in the developing auditory system are glutamatergic. Nat Neurosci. 2005;8:332-8 pubmed
    ..Synapse-specific activation of NMDARs by glutamate release at GABAergic and glycinergic synapses could be important in activity-dependent refinement of inhibitory circuits. ..
  9. Boulland J, Qureshi T, Seal R, Rafiki A, Gundersen V, Bergersen L, et al. Expression of the vesicular glutamate transporters during development indicates the widespread corelease of multiple neurotransmitters. J Comp Neurol. 2004;480:264-80 pubmed
    ..In skeletal muscle, VGLUT3 localizes to granular organelles in the axon terminal as well as in the muscle sarcoplasm. The results suggest novel mechanisms and roles for regulated transmitter release. ..

More Information


  1. Fremeau R, Voglmaier S, Seal R, Edwards R. VGLUTs define subsets of excitatory neurons and suggest novel roles for glutamate. Trends Neurosci. 2004;27:98-103 pubmed
    ..VGLUT3 also differs from VGLUT1 and VGLUT2 in its subcellular location, with somatodendritic as well as axonal expression. ..
  2. Montana V, Ni Y, Sunjara V, Hua X, Parpura V. Vesicular glutamate transporter-dependent glutamate release from astrocytes. J Neurosci. 2004;24:2633-42 pubmed
    ..Taken together, these data indicate that VGLUTs play a functional role in exocytotic glutamate release from astrocytes. ..
  3. Kariv Inbal Z, Yacobson S, Berkecz R, Peter M, Janaky T, Lutjohann D, et al. The isoform-specific pathological effects of apoE4 in vivo are prevented by a fish oil (DHA) diet and are modified by cholesterol. J Alzheimers Dis. 2012;28:667-83 pubmed publisher
    ..Importantly, all of these apoE4 phenotypes were abolished by the fish oil (DHA) diet, whereas the cholesterol diet modified them. These findings suggest that a fish oil (DHA) diet could be used to attenuate the effects of apoE4 in AD. ..
  4. Oliveira A, Hydling F, Olsson E, Shi T, Edwards R, Fujiyama F, et al. Cellular localization of three vesicular glutamate transporter mRNAs and proteins in rat spinal cord and dorsal root ganglia. Synapse. 2003;50:117-29 pubmed
    ..VGLUT1 is mainly present in primary afferents from large, CGRP-negative DRG neurons, VGLUT2 has mainly a local origin, and VGLUT3 fibers probably have a supraspinal origin. ..
  5. Villar Cerviño V, Rocancourt C, Menuet A, Da Silva C, Wincker P, Anadón R, et al. A vesicular glutamate transporter in lampreys: cDNA cloning and early expression in the nervous system. J Chem Neuroanat. 2010;40:71-81 pubmed publisher
    ..Comparison of the early expression of VGluT genes between the lamprey and some anamniotan gnathostomes (frog, zebrafish) reveals a conserved expression pattern, likely to reflect ancestral vertebrate characteristics...
  6. Schafer M, Varoqui H, Defamie N, Weihe E, Erickson J. Molecular cloning and functional identification of mouse vesicular glutamate transporter 3 and its expression in subsets of novel excitatory neurons. J Biol Chem. 2002;277:50734-48 pubmed
  7. Chung E, Chen L, Chan Y, Yung K. Up-regulation in expression of vesicular glutamate transporter 3 in substantia nigra but not in striatum of 6-hydroxydopamine-lesioned rats. Neurosignals. 2006;15:238-48 pubmed
    ..The present results may therefore implicate that VGLUT1 and T2 are not modulated in the striatum and the substantia nigra of the 6-hydroxydopamine-lesioned rat and only VGLUT3 plays a role in pathogenesis of Parkinson's disease. ..
  8. Gras C, Herzog E, Bellenchi G, Bernard V, Ravassard P, Pohl M, et al. A third vesicular glutamate transporter expressed by cholinergic and serotoninergic neurons. J Neurosci. 2002;22:5442-51 pubmed
    ..Our study reveals a novel class of glutamatergic nerve terminals and suggests that cholinergic striatal interneurons and serotoninergic neurons from the brainstem may store and release glutamate. ..
  9. Landry M, Bouali Benazzouz R, El Mestikawy S, Ravassard P, Nagy F. Expression of vesicular glutamate transporters in rat lumbar spinal cord, with a note on dorsal root ganglia. J Comp Neurol. 2004;468:380-94 pubmed
  10. Herzog E, Gilchrist J, Gras C, Muzerelle A, Ravassard P, Giros B, et al. Localization of VGLUT3, the vesicular glutamate transporter type 3, in the rat brain. Neuroscience. 2004;123:983-1002 pubmed
    ..The distribution of VGLUT3 in the rat brain suggests an unsuspected function of vesicular glutamate transport in subsets of interneurons and in neuromodulatory neurons. ..
  11. Takamori S. VGLUTs: 'exciting' times for glutamatergic research?. Neurosci Res. 2006;55:343-51 pubmed
  12. Wojcik S, Rhee J, Herzog E, Sigler A, Jahn R, Takamori S, et al. An essential role for vesicular glutamate transporter 1 (VGLUT1) in postnatal development and control of quantal size. Proc Natl Acad Sci U S A. 2004;101:7158-63 pubmed
    ..These results show that the expression level of VGLUTs determines the amount of glutamate that is loaded into vesicles and released and thereby regulates the efficacy of neurotransmission. ..
  13. Steinert J, Kuromi H, Hellwig A, Knirr M, Wyatt A, Kidokoro Y, et al. Experience-dependent formation and recruitment of large vesicles from reserve pool. Neuron. 2006;50:723-33 pubmed
    ..Our results demonstrate that natural behavior can induce the formation, recruitment, and release of larger vesicles in an experience-dependent manner and hence provide evidence for an additional mechanism of synaptic potentiation. ..
  14. El Mestikawy S, Wallén Mackenzie A, Fortin G, Descarries L, Trudeau L. From glutamate co-release to vesicular synergy: vesicular glutamate transporters. Nat Rev Neurosci. 2011;12:204-16 pubmed publisher
    ..The behavioural relevance of this co-phenotype is presently the focus of considerable interest. ..
  15. Omote H, Miyaji T, Juge N, Moriyama Y. Vesicular neurotransmitter transporter: bioenergetics and regulation of glutamate transport. Biochemistry. 2011;50:5558-65 pubmed publisher
    ..These results suggest a correlation between metabolic state and higher-order brain function. We propose a novel function for Cl(-) as a fundamental regulator for signal transmission. ..
  16. Chomsung R, Petry H, Bickford M. Ultrastructural examination of diffuse and specific tectopulvinar projections in the tree shrew. J Comp Neurol. 2008;510:24-46 pubmed publisher
    ..These results provide strong evidence for the division of the tree shrew pulvinar into two distinct tectorecipient zones. The potential functions of these pathways are discussed. ..
  17. Villar Cerviño V, Barreiro Iglesias A, Mazan S, Rodicio M, Anadón R. Glutamatergic neuronal populations in the forebrain of the sea lamprey, Petromyzon marinus: an in situ hybridization and immunocytochemical study. J Comp Neurol. 2011;519:1712-35 pubmed publisher
    ..Comparison with glutamatergic cells observed in rodent forebrains suggests that the regional distribution of glutamatergic cells does not differ greatly in lampreys and mammals...
  18. Fei H, Karnezis T, Reimer R, Krantz D. Membrane topology of the Drosophila vesicular glutamate transporter. J Neurochem. 2007;101:1662-71 pubmed
    ..Lumenal domains include sequences between TMs 1-2, 3-4, 5-6, 7-8 and 9-10. These data provide a basis for determining structure-function relationships for DVGLUT and other related proteins. ..
  19. Fremeau R, Burman J, Qureshi T, Tran C, Proctor J, Johnson J, et al. The identification of vesicular glutamate transporter 3 suggests novel modes of signaling by glutamate. Proc Natl Acad Sci U S A. 2002;99:14488-93 pubmed
    ..The dendritic expression of VGLUT3 by particular neurons also indicates the potential for retrograde synaptic signaling. The distribution and subcellular location of VGLUT3 thus suggest novel modes of signaling by glutamate. ..
  20. Somogyi J, Baude A, Omori Y, Shimizu H, El Mestikawy S, Fukaya M, et al. GABAergic basket cells expressing cholecystokinin contain vesicular glutamate transporter type 3 (VGLUT3) in their synaptic terminals in hippocampus and isocortex of the rat. Eur J Neurosci. 2004;19:552-69 pubmed
    ..The presumed amino acid substrate of VGLUT3 may act on presynaptic kainate or group II metabotropic glutamate receptors. ..
  21. Daniels R, Collins C, Chen K, Gelfand M, Featherstone D, DiAntonio A. A single vesicular glutamate transporter is sufficient to fill a synaptic vesicle. Neuron. 2006;49:11-6 pubmed
    ..Consistent with the presence of empty vesicles, at dvglut mutant synapses synaptic vesicles are smaller, suggesting that vesicle filling and/or transporter level is an important determinant of vesicle size. ..
  22. Yang C, Wei Y, Leng Y, Zhong C, Zhang Y, Wan Y, et al. Vesicular glutamate transporter-3 contributes to visceral hyperalgesia induced by Trichinella spiralis infection in rats. Dig Dis Sci. 2012;57:865-72 pubmed publisher
    ..VGLUT3 is involved in conduction of visceral pain sensation and in visceral hyperalgesia induced by Trichinella spiralis infection in rats. ..
  23. Wang H, Morales M. Pedunculopontine and laterodorsal tegmental nuclei contain distinct populations of cholinergic, glutamatergic and GABAergic neurons in the rat. Eur J Neurosci. 2009;29:340-58 pubmed publisher
  24. Rodriguez Contreras A, de Lange R, Lucassen P, Borst J. Branching of calyceal afferents during postnatal development in the rat auditory brainstem. J Comp Neurol. 2006;496:214-28 pubmed
    ..Our data suggest that, once a calyceal synapse forms in the MNTB, it stays. ..
  25. Santos M, D Amico D, Spadoni O, Amador Arjona A, Stork O, Dierssen M. Hippocampal hyperexcitability underlies enhanced fear memories in TgNTRK3, a panic disorder mouse model. J Neurosci. 2013;33:15259-71 pubmed publisher
    ..The fearful phenotype appears to be the result of hippocampal hyperexcitability and aberrant fear circuit activation. We conclude that NTRK3 plays a role in PAND by regulating hippocampus-dependent fear memories. ..
  26. Osikowicz M, Mika J, Przewlocka B. The glutamatergic system as a target for neuropathic pain relief. Exp Physiol. 2013;98:372-84 pubmed publisher
    ..Additionally, the question of how the modulation of the glutamatergic system influences the effectiveness of analgesic drugs used in neuropathic pain therapy is addressed. ..
  27. Krantz D. Vesicular monogamy?. Neuron. 2006;49:1-2 pubmed
    ..In this issue of Neuron, a study by Daniels et al. using the Drosophila neuromuscular junction and mutations of the vesicular glutamate transporter suggests that one transporter may suffice to fill each vesicle. ..
  28. Paluzzi S, Alloisio S, Zappettini S, Milanese M, Raiteri L, Nobile M, et al. Adult astroglia is competent for Na+/Ca2+ exchanger-operated exocytotic glutamate release triggered by mild depolarization. J Neurochem. 2007;103:1196-207 pubmed
    ..To conclude, depolarization triggers in vitro glutamate exocytosis from in situ matured adult astrocytes; an aptitude grounding on Ca2+ influx driven by the Na+/Ca2+ exchanger working in the reverse mode. ..
  29. Lin L. Glutamatergic neurons say NO in the nucleus tractus solitarii. J Chem Neuroanat. 2009;38:154-65 pubmed publisher
    ..Thus, taken together, these neuroanatomical data support the hypothesis that glutamate and NO may interact with each other to regulate cardiovascular and likely other visceral functions through the NTS. ..
  30. Gritti I, Henny P, Galloni F, Mainville L, Mariotti M, Jones B. Stereological estimates of the basal forebrain cell population in the rat, including neurons containing choline acetyltransferase, glutamic acid decarboxylase or phosphate-activated glutaminase and colocalizing vesicular glutamate transporters. Neuroscience. 2006;143:1051-64 pubmed
  31. Hioki H, Nakamura H, Ma Y, Konno M, Hayakawa T, Nakamura K, et al. Vesicular glutamate transporter 3-expressing nonserotonergic projection neurons constitute a subregion in the rat midbrain raphe nuclei. J Comp Neurol. 2010;518:668-86 pubmed publisher
    ..These results suggest that VGLUT3-expressing nonserotonergic neurons in the midbrain raphe nuclei are preferentially distributed in the DRDSh and modulate many brain regions with the neurotransmitter glutamate via ascending axons. ..
  32. Li D, Hérault K, Silm K, Evrard A, Wojcik S, Oheim M, et al. Lack of evidence for vesicular glutamate transporter expression in mouse astrocytes. J Neurosci. 2013;33:4434-55 pubmed publisher
    ..Our data provide no evidence in favor of the expression of any of the three VGLUTs by gray matter protoplasmic astrocytes of the primary somatosensory cortex, the thalamic ventrobasal nucleus, the hippocampus, and the cerebellum. ..
  33. Hamilton N, Attwell D. Do astrocytes really exocytose neurotransmitters?. Nat Rev Neurosci. 2010;11:227-38 pubmed publisher
    ..However, there is intense controversy about whether astrocytes can exocytose transmitters in vivo. Resolving this issue would considerably advance our understanding of brain function. ..
  34. Mohrmann R, Matthies H, Woodruff E, Broadie K. Stoned B mediates sorting of integral synaptic vesicle proteins. Neuroscience. 2008;153:1048-63 pubmed publisher
    ..We conclude that STNB organizes the endocytic sorting of a subset of integral synaptic vesicle proteins thereby regulating the fusion-competence of the recycled vesicle. ..
  35. Dutta R, Chang A, Doud M, Kidd G, Ribaudo M, Young E, et al. Demyelination causes synaptic alterations in hippocampi from multiple sclerosis patients. Ann Neurol. 2011;69:445-54 pubmed publisher
    ..Collectively, these data support hippocampal demyelination as a cause of synaptic alterations in MS patients and establish that the neuronal genes regulated by myelination reflect specific functions of neuronal subpopulations. ..
  36. Mishra M, Kumawat K, Basu A. Japanese encephalitis virus differentially modulates the induction of multiple pro-inflammatory mediators in human astrocytoma and astroglioma cell-lines. Cell Biol Int. 2008;32:1506-13 pubmed publisher
  37. Malet M, Brumovsky P. VGLUTs and Glutamate Synthesis-Focus on DRG Neurons and Pain. Biomolecules. 2015;5:3416-37 pubmed publisher
    ..The possible interplay between glutamate biosynthesis and VGLUT-dependent packaging in synaptic vesicles, and its potential impact in various pain states will be presented. ..
  38. Zanazzi G, Matthews G. The molecular architecture of ribbon presynaptic terminals. Mol Neurobiol. 2009;39:130-48 pubmed publisher
    ..Consistent with its functional importance, abnormalities in a variety of functional aspects of the ribbon presynaptic terminal underlie several forms of auditory neuropathy and retinopathy. ..
  39. Lin L, Talman W. Vesicular glutamate transporters and neuronal nitric oxide synthase colocalize in aortic depressor afferent neurons. J Chem Neuroanat. 2006;32:54-64 pubmed
    ..These results support our hypothesis and suggest prominent roles of VGLUT2-IR containing neurons and VGLUT3-IR containing neurons in transmitting cardiovascular signals via the ADN to the brain stem. ..
  40. Ulu M, Tanriverdi T, Oz B, Biceroglu H, Isler C, Eraslan B, et al. The expression of astroglial glutamate transporters in patients with focal cortical dysplasia: an immunohistochemical study. Acta Neurochir (Wien). 2010;152:845-53 pubmed publisher
    ..Further studies with larger patient populations,investigating the expression of glutamate transporters at mRNA and protein levels, are required to clarify their roles in the pathophysiology of FCD. ..
  41. Cai Y, Ma W, Wang J, Li Y, Li M. Excitatory pathways from the vestibular nuclei to the NTS and the PBN and indirect vestibulo-cardiovascular pathway from the vestibular nuclei to the RVLM relayed by the NTS. Brain Res. 2008;1240:96-104 pubmed publisher
    ..The glutamatergic VN-NTS and VN-PBN pathways might exist, and the projections from the VN to the RVLM relayed by the NTS comprise an indirect vestibulo-cardiovascular pathway in the brain stem. ..
  42. Tashiro Y, Okada T, Kawai Y. Postnatal development of axosomatic synapses in the rat nucleus tractus solitarius: dorsal and ventral subnuclei differences. Neurosci Lett. 2009;450:217-20 pubmed publisher
  43. Palygin O, Lalo U, Pankratov Y. Distinct pharmacological and functional properties of NMDA receptors in mouse cortical astrocytes. Br J Pharmacol. 2011;163:1755-66 pubmed publisher
    ..Our results may also provide the basis for the development of novel therapeutic agents specifically targeting glial signalling. ..
  44. Nunzi M, Pisarek A, Mugnaini E. Merkel cells, corpuscular nerve endings and free nerve endings in the mouse palatine mucosa express three subtypes of vesicular glutamate transporters. J Neurocytol. 2004;33:359-76 pubmed
    ..The data suggest that glutamate release, or co-release, is likely to represent an important functional aspect of palatine Merkel cells and neighboring corpuscular and free nerve endings. ..
  45. Kirvell S, Esiri M, Francis P. Down-regulation of vesicular glutamate transporters precedes cell loss and pathology in Alzheimer's disease. J Neurochem. 2006;98:939-50 pubmed publisher
    ..These changes were found to relate to the number of tangles in the temporal cortex. There were no correlations with either mental test score or behaviour syndromes, with the exception of depression...
  46. Balland B, Lachamp P, Kessler J, Tell F. Silent synapses in developing rat nucleus tractus solitarii have AMPA receptors. J Neurosci. 2008;28:4624-34 pubmed publisher
    ..Glutamate spillover at immature NTS synapses may favor crosstalk between active synapses during development when glutamate transporters are weakly expressed and contribute to synaptic processing as well as autonomic circuit formation. ..
  47. Zerari Mailly F, Braud A, Davido N, Touré B, Azerad J, Boucher Y. Glutamate control of pulpal blood flow in the incisor dental pulp of the rat. Eur J Oral Sci. 2012;120:402-7 pubmed publisher
    ..Also, VGluT3 was colocalized with the vascular marker SMA, and in some nerve fibers with IB4, but not with CGRP. This study provides support for a control of dental pulp microcirculation by neurons expressing VGluT3. ..
  48. Sasaki T, Komatsu Y, Watakabe A, Sawada K, Yamamori T. Prefrontal-enriched SLIT1 expression in Old World monkey cortex established during the postnatal development. Cereb Cortex. 2010;20:2496-510 pubmed publisher
    ..These results suggest that its role is altered postnatally and that this is particularly important for prefrontal connectivity in the Old World monkey cortex. ..
  49. Gordon S, Cousin M. X-linked intellectual disability-associated mutations in synaptophysin disrupt synaptobrevin II retrieval. J Neurosci. 2013;33:13695-700 pubmed publisher
  50. Kindlundh Högberg A, Blomqvist A, Malki R, Schioth H. Extensive neuroadaptive changes in cortical gene-transcript expressions of the glutamate system in response to repeated intermittent MDMA administration in adolescent rats. BMC Neurosci. 2008;9:39 pubmed publisher
  51. Lasztóczi B, Tukker J, Somogyi P, Klausberger T. Terminal field and firing selectivity of cholecystokinin-expressing interneurons in the hippocampal CA3 area. J Neurosci. 2011;31:18073-93 pubmed publisher
  52. Chi D, Kandler K. Cannabinoid receptor expression at the MNTB-LSO synapse in developing rats. Neurosci Lett. 2012;509:96-100 pubmed publisher
    ..These results suggest that endocannabinoid signaling can modulate the strength of the developing MNTB-LSO synapse. ..
  53. Zhang L, Parks G, Wang Z, Wang L, Lew M, Civelli O. Anatomical characterization of bombesin receptor subtype-3 mRNA expression in the rodent central nervous system. J Comp Neurol. 2013;521:1020-39 pubmed publisher
    ..Our study provides important information for evaluating BRS-3 as a potential therapeutic target for the treatment of obesity. ..