vesicular acetylcholine transport proteins


Summary: Vesicular amine transporter proteins that transport the neurotransmitter ACETYLCHOLINE into small SECRETORY VESICLES. Proteins of this family contain 12 transmembrane domains and exchange vesicular PROTONS for cytoplasmic acetylcholine.

Top Publications

  1. Lima R, Prado V, Prado M, Kushmerick C. Quantal release of acetylcholine in mice with reduced levels of the vesicular acetylcholine transporter. J Neurochem. 2010;113:943-51 pubmed publisher
    ..These results reveal the dependence of short-term plasticity on the level of VAChT expression and efficient synaptic vesicle filling. ..
  2. Schütz B, Damadzic R, Weihe E, Eiden L. Identification of a region from the human cholinergic gene locus that targets expression of the vesicular acetylcholine transporter to a subset of neurons in the medial habenular nucleus in transgenic mice. J Neurochem. 2003;87:1174-83 pubmed
    ..The identification of these two subdivisions of the cholinergic nervous system suggests that other cholinergic neurons in the CNS and PNS are similarly regulated by additional discrete domains within the cholinergic gene locus. ..
  3. Alfonso A, Grundahl K, Duerr J, Han H, Rand J. The Caenorhabditis elegans unc-17 gene: a putative vesicular acetylcholine transporter. Science. 1993;261:617-9 pubmed
    ..The mutants will also be useful for the isolation of extragenic suppressors, which could identify genes encoding proteins that interact with UNC-17. ..
  4. Gras C, Amilhon B, Lepicard E, Poirel O, Vinatier J, Herbin M, et al. The vesicular glutamate transporter VGLUT3 synergizes striatal acetylcholine tone. Nat Neurosci. 2008;11:292-300 pubmed publisher
    ..Our study reveals a previously unknown effect of glutamate on cholinergic synapses with potential functional and pharmacological implications. ..
  5. de Castro B, Pereira G, Magalhaes V, Rossato J, De Jaeger X, Martins Silva C, et al. Reduced expression of the vesicular acetylcholine transporter causes learning deficits in mice. Genes Brain Behav. 2009;8:23-35 pubmed publisher
    ..These data indicate an important role for cholinergic tone in motor learning and object recognition memory. ..
  6. Naciff J, Behbehani M, Misawa H, Dedman J. Identification and transgenic analysis of a murine promoter that targets cholinergic neuron expression. J Neurochem. 1999;72:17-28 pubmed
  7. Prado V, Martins Silva C, de Castro B, Lima R, Barros D, Amaral E, et al. Mice deficient for the vesicular acetylcholine transporter are myasthenic and have deficits in object and social recognition. Neuron. 2006;51:601-12 pubmed
    ..These observations suggest a critical role of VAChT in the regulation of ACh release and physiological functions in the peripheral and central nervous system. ..
  8. Martyn A, De Jaeger X, Magalhaes A, Kesarwani R, Gonçalves D, Raulic S, et al. Elimination of the vesicular acetylcholine transporter in the forebrain causes hyperactivity and deficits in spatial memory and long-term potentiation. Proc Natl Acad Sci U S A. 2012;109:17651-6 pubmed publisher
    ..These data uncover the specific contribution of forebrain cholinergic tone for synaptic plasticity and behavior. Moreover, these experiments define specific cognitive functions that could be targeted by cholinergic replacement therapy. ..
  9. Danielson P, Alfredson H, Forsgren S. Immunohistochemical and histochemical findings favoring the occurrence of autocrine/paracrine as well as nerve-related cholinergic effects in chronic painful patellar tendon tendinosis. Microsc Res Tech. 2006;69:808-19 pubmed
    ..Thus, in conclusion, there appears to be an upregulation of the cholinergic system, and an occurrence of autocrine/paracrine effects in this system, in the tendinosis patellar tendon. ..

More Information


  1. Guzman M, De Jaeger X, Raulic S, Souza I, Li A, Schmid S, et al. Elimination of the vesicular acetylcholine transporter in the striatum reveals regulation of behaviour by cholinergic-glutamatergic co-transmission. PLoS Biol. 2011;9:e1001194 pubmed publisher
    ..The data also raise the possibility of using VAChT as a target to boost dopaminergic function and decrease high striatal cholinergic activity, common neurochemical alterations in individuals affected with Parkinson's disease. ..
  2. Zagoraiou L, Akay T, Martin J, Brownstone R, Jessell T, Miles G. A cluster of cholinergic premotor interneurons modulates mouse locomotor activity. Neuron. 2009;64:645-62 pubmed publisher
    ..Thus, V0(C) interneurons represent a defined class of spinal cholinergic interneurons with an intrinsic neuromodulatory role in the control of locomotor behavior. ..
  3. Martins Silva C, De Jaeger X, Guzman M, Lima R, Santos M, Kushmerick C, et al. Novel strains of mice deficient for the vesicular acetylcholine transporter: insights on transcriptional regulation and control of locomotor behavior. PLoS ONE. 2011;6:e17611 pubmed publisher
    ..These results suggest that release of ACh in the brain is normally required to "turn down" neuronal circuits controlling locomotion. ..
  4. Prado V, Prado M. Signals involved in targeting membrane proteins to synaptic vesicles. Cell Mol Neurobiol. 2002;22:565-77 pubmed
    ..We suggest that the vesicular acetylcholine transporter, a protein found predominantly in synaptic vesicles, is perhaps a model protein to understand the pathways and interactions that are used for synaptic vesicle targeting. ..
  5. Huberman A, Wang G, Liets L, Collins O, Chapman B, Chalupa L. Eye-specific retinogeniculate segregation independent of normal neuronal activity. Science. 2003;300:994-8 pubmed
    ..Thus, certain features of normal neural activity patterns are not required for the formation of eye-specific projections to the DLGN. ..
  6. Khare P, White A, Parsons S. Multiple protonation states of vesicular acetylcholine transporter detected by binding of [3H]vesamicol. Biochemistry. 2009;48:8965-75 pubmed publisher
    ..The potential significance of the findings to development of PET and SPECT ligands based on (-)-vesamicol for human diagnostics also is discussed. ..
  7. Kim M, Hersh L. The vesicular acetylcholine transporter interacts with clathrin-associated adaptor complexes AP-1 and AP-2. J Biol Chem. 2004;279:12580-7 pubmed
    ..There appear to be two endocytosis motifs, one involving the adaptor protein 1 binding site and the other involving the adaptor protein 2 binding site. These results suggest a complex trafficking pathway for VAChT. ..
  8. Lara A, Damasceno D, Pires R, Gros R, Gomes E, Gavioli M, et al. Dysautonomia due to reduced cholinergic neurotransmission causes cardiac remodeling and heart failure. Mol Cell Biol. 2010;30:1746-56 pubmed publisher
    ..Our findings provide direct evidence that decreased cholinergic neurotransmission and underlying autonomic imbalance cause plastic alterations that contribute to heart dysfunction. ..
  9. Huberman A, Manu M, Koch S, Susman M, Lutz A, Ullian E, et al. Architecture and activity-mediated refinement of axonal projections from a mosaic of genetically identified retinal ganglion cells. Neuron. 2008;59:425-38 pubmed publisher
    ..Our findings reveal that in a genetically identified sensory map, spontaneous activity promotes synaptic specificity by segregating axons arising from RGCs of the same subtype. ..
  10. Gould T, Yonemura S, Oppenheim R, Ohmori S, Enomoto H. The neurotrophic effects of glial cell line-derived neurotrophic factor on spinal motoneurons are restricted to fusimotor subtypes. J Neurosci. 2008;28:2131-46 pubmed publisher
    ..Therefore, although GDNF influences several aspects of MN development, the survival-promoting effects of GDNF during programmed cell death are mostly confined to spindle-innervating MNs. ..
  11. Ribeiro F, Alves Silva J, Volknandt W, Martins Silva C, Mahmud H, Wilhelm A, et al. The hemicholinium-3 sensitive high affinity choline transporter is internalized by clathrin-mediated endocytosis and is present in endosomes and synaptic vesicles. J Neurochem. 2003;87:136-46 pubmed
    ..We propose that intracellular CHT1 can be recruited during stimulation to increase choline uptake in nerve terminals...
  12. 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. ..
  13. Schmid S, Azzopardi E, De Jaeger X, Prado M, Prado V. VAChT knock-down mice show normal prepulse inhibition but disrupted long-term habituation. Genes Brain Behav. 2011;10:457-64 pubmed publisher
    ..The disruption of LTH indicates that the latter depends on a tonic cholinergic inhibition. Future experiments will address which cholinergic cell group is responsible for this effect. ..
  14. Barbosa J, Ferreira L, Martins Silva C, Santos M, Torres G, Caron M, et al. Trafficking of the vesicular acetylcholine transporter in SN56 cells: a dynamin-sensitive step and interaction with the AP-2 adaptor complex. J Neurochem. 2002;82:1221-8 pubmed
    ..These observations suggest that the di-leucine motif regulates sorting of VAChT from the soma plasma membrane through a clathrin dependent mechanism prior to the targeting of the transporter to varicosities. ..
  15. Schutz B, Chen L, Schafer M, Weihe E, Eiden L. Somatomotor neuron-specific expression of the human cholinergic gene locus in transgenic mice. Neuroscience. 2000;96:707-22 pubmed
  16. Prado V, Roy A, Kolisnyk B, Gros R, Prado M. Regulation of cholinergic activity by the vesicular acetylcholine transporter. Biochem J. 2013;450:265-74 pubmed publisher
    ..Hence novel functions for the oldest neurotransmitter known are emerging with the potential to provide new targets for the treatment of several pathological conditions. ..
  17. Parsons S. Transport mechanisms in acetylcholine and monoamine storage. FASEB J. 2000;14:2423-34 pubmed
    ..Comparative analysis of the VAChT and VMAT transport mechanisms will aid understanding of regulation in neurotransmitter storage. ..
  18. Kitamoto T, Wang W, Salvaterra P. Structure and organization of the Drosophila cholinergic locus. J Biol Chem. 1998;273:2706-13 pubmed
    ..These features of the VAChT 5'-UTR region suggest that a ribosome scanning model may not be used for VAChT translation initiation. ..
  19. Eiden L. The cholinergic gene locus. J Neurochem. 1998;70:2227-40 pubmed
    ..These advances should accelerate the development of "cholinergic" pharmacological and gene therapeutic approaches to treatment of human diseases that are associated with cholinergic surfeit and insufficiency. ..
  20. Erickson J, Varoqui H, Schafer M, Modi W, Diebler M, Weihe E, et al. Functional identification of a vesicular acetylcholine transporter and its expression from a "cholinergic" gene locus. J Biol Chem. 1994;269:21929-32 pubmed
  21. Danielson P, Andersson G, Alfredson H, Forsgren S. Extensive expression of markers for acetylcholine synthesis and of M2 receptors in tenocytes in therapy-resistant chronic painful patellar tendon tendinosis - a pilot study. Life Sci. 2007;80:2235-8 pubmed
    ..Thus, the results of this pilot study suggest that non-neuronal ACh is highly involved in the pathology of therapy-resistant patellar tendinosis. ..
  22. Smith R, Chung H, Rundquist S, Maat Schieman M, Colgan L, Englund E, et al. Cholinergic neuronal defect without cell loss in Huntington's disease. Hum Mol Genet. 2006;15:3119-31 pubmed
    ..Taken together, our data show that the cholinergic system is dysfunctional in R6/1 and HD patients. Consequently, they provide a rationale for testing of pro-cholinergic drugs in this disease. ..
  23. Kakinuma Y, Akiyama T, Sato T. Cholinoceptive and cholinergic properties of cardiomyocytes involving an amplification mechanism for vagal efferent effects in sparsely innervated ventricular myocardium. FEBS J. 2009;276:5111-25 pubmed publisher
    ..Such an amplification system in cardiomyocytes may contribute to the beneficial effects of vagal stimulation on the ventricles. ..
  24. Ferreira L, Santos M, Kolmakova N, Koenen J, Barbosa J, Gomez M, et al. Structural requirements for steady-state localization of the vesicular acetylcholine transporter. J Neurochem. 2005;94:957-69 pubmed
    ..The data provide novel information on the mechanisms and structural determinants necessary for VAChT localization to synaptic vesicles. ..
  25. Bravo D, Kolmakova N, Parsons S. Mutational and pH analysis of ionic residues in transmembrane domains of vesicular acetylcholine transporter. Biochemistry. 2005;44:7955-66 pubmed
    ..The pH effects also indicate that sites that must be unprotonated for transport (apparent pK(a) approximately 6.4) and vesamicol binding (apparent pK(a) approximately 6.3) remain unidentified. ..
  26. Brauchi S, Krapivinsky G, Krapivinsky L, Clapham D. TRPM7 facilitates cholinergic vesicle fusion with the plasma membrane. Proc Natl Acad Sci U S A. 2008;105:8304-8 pubmed publisher
    ..We conclude that the conductance of TRPM7 across the vesicle membrane is important in SSLV fusion. ..
  27. Capettini S, Moraes M, Prado V, Prado M, Pereira G. Vesicular acetylcholine transporter knock-down mice show sexual dimorphism on memory. Brain Res Bull. 2011;85:54-7 pubmed publisher
    ..Our results strongly suggest that the sexual dimorphism observed in VAChT KDHET mice on STM is due to modulation of cholinergic system by ovarian hormones. ..
  28. Guidine P, Rezende G, Queiroz C, Mello L, Prado V, Prado M, et al. Vesicular acetylcholine transporter knock-down mice are more susceptible to pilocarpine induced status epilepticus. Neurosci Lett. 2008;436:201-4 pubmed publisher
    ..Thus, fine-tuning modulation of cholinergic tone can affect the susceptibility of epileptic responses to pilocarpine. ..
  29. Misawa H, Nakata K, Toda K, Matsuura J, Oda Y, Inoue H, et al. VAChT-Cre. Fast and VAChT-Cre.Slow: postnatal expression of Cre recombinase in somatomotor neurons with different onset. Genesis. 2003;37:44-50 pubmed
    ..The use of VAChT-Cre mice should allow us to deliver Cre to a subset of postnatal motor neurons, thereby bypassing lethality and facilitating analysis of gene function in adult motor neurons. ..
  30. de Castro B, De Jaeger X, Martins Silva C, Lima R, Amaral E, Menezes C, et al. The vesicular acetylcholine transporter is required for neuromuscular development and function. Mol Cell Biol. 2009;29:5238-50 pubmed publisher
    ..The abnormalities are similar to those of mice that cannot synthesize ACh due to a lack of choline acetyltransferase. Our results indicate that VAChT is essential to the normal development of motor neurons and the release of ACh. ..
  31. Cervini R, Houhou L, Pradat P, Bejanin S, Mallet J, Berrard S. Specific vesicular acetylcholine transporter promoters lie within the first intron of the rat choline acetyltransferase gene. J Biol Chem. 1995;270:24654-7 pubmed
    ..Two VAChT mRNAs are generated from these promoters. These results demonstrate that the promoter regions of these two genes are intermingled, which highlight the unique organization of the ChAT/VAChT gene locus. ..
  32. Ojeda A, Kolmakova N, Parsons S. Acetylcholine binding site in the vesicular acetylcholine transporter. Biochemistry. 2004;43:11163-74 pubmed
    ..Results also are discussed in terms of recently determined three-dimensional structures for other transporters in the major facilitator superfamily. ..
  33. Kawamura K, Shiba K, Tsukada H, Nishiyama S, Mori H, Ishiwata K. Synthesis and evaluation of vesamicol analog (-)-O-[11C]methylvesamicol as a PET ligand for vesicular acetylcholine transporter. Ann Nucl Med. 2006;20:417-24 pubmed
    ..Therefore, (-)-[11C]OMV-PET together with help of [11C]SA4503-PET may evaluate VAChTs. ..
  34. Fernando R, Larm J, Albiston A, Chai S. Distribution and cellular localization of insulin-regulated aminopeptidase in the rat central nervous system. J Comp Neurol. 2005;487:372-90 pubmed
  35. Irie T, Fukui I, Ohmori H. Activation of GIRK channels by muscarinic receptors and group II metabotropic glutamate receptors suppresses Golgi cell activity in the cochlear nucleus of mice. J Neurophysiol. 2006;96:2633-44 pubmed
  36. Kallmünzer B, Sörensen B, Neuhuber W, Wörl J. Heterogeneity of neuromuscular junctions in striated muscle of human esophagus demonstrated by triple staining for the vesicular acetylcholine transporter, alpha-bungarotoxin, and acetylcholinesterase. Cell Tissue Res. 2006;324:181-8 pubmed
  37. Pawlowski S, Gaillard S, Ghorayeb I, Ribeiro Da Silva A, Schlichter R, Cordero Erausquin M. A novel population of cholinergic neurons in the macaque spinal dorsal horn of potential clinical relevance for pain therapy. J Neurosci. 2013;33:3727-37 pubmed publisher
  38. Kozaka T, Uno I, Kitamura Y, Miwa D, Ogawa K, Shiba K. Syntheses and in vitro evaluation of decalinvesamicol analogues as potential imaging probes for vesicular acetylcholine transporter (VAChT). Bioorg Med Chem. 2012;20:4936-41 pubmed publisher
    ..In addition, BBB penetration of [(125)I]OIDV was verified in in vivo. The results of the binding studies indicated that OIDV and OBDV had great potential to be VAChT imaging probes with high affinity and selectivity. ..
  39. Gunhan E, Choudary P, Landerholm T, Chalupa L. Depletion of cholinergic amacrine cells by a novel immunotoxin does not perturb the formation of segregated on and off cone bipolar cell projections. J Neurosci. 2002;22:2265-73 pubmed
    ..These findings demonstrate that the presence of cholinergic amacrine cells is not required for the segregation of recoverin-positive On and Off cone bipolar cell projections. ..
  40. Boucetta S, Cisse Y, Mainville L, Morales M, Jones B. Discharge profiles across the sleep-waking cycle of identified cholinergic, GABAergic, and glutamatergic neurons in the pontomesencephalic tegmentum of the rat. J Neurosci. 2014;34:4708-27 pubmed publisher
  41. Gamo K, Kiryu Seo S, Yoshikawa H, Kiyama H. Suture of transected nerve suppresses expression of BH3-only protein Noxa in nerve-transected motor neurons of C57BL/6J mouse. J Neurotrauma. 2007;24:876-84 pubmed
    ..A significant suppression of Noxa expression by the Suture may be a major reason why nerve suture induces survival and regeneration of nerve-injured motor neurons. ..
  42. Cellek S, Anderson P, Foxwell N. Nitrergic neurodegeneration in cerebral arteries of streptozotocin-induced diabetic rats: a new insight into diabetic stroke. Diabetes. 2005;54:212-9 pubmed
    ..This is the first demonstration of nitrergic degeneration in diabetic cerebral arteries, which could elucidate the link between diabetic autonomic neuropathy and stroke. ..
  43. Phillips P, Yang L, Shulkes A, Vonlaufen A, Poljak A, Bustamante S, et al. Pancreatic stellate cells produce acetylcholine and may play a role in pancreatic exocrine secretion. Proc Natl Acad Sci U S A. 2010;107:17397-402 pubmed publisher
    ..CCK stimulates ACh secretion by PSCs, which, in turn, induces amylase secretion by acini. Therefore, PSCs may represent a previously unrecognized intrapancreatic pathway regulating CCK-induced pancreatic exocrine secretion...
  44. Efange S, Khare A, Mach R, Parsons S. Hydroxylated decahydroquinolines as ligands for the vesicular acetylcholine transporter: synthesis and biological evaluation. J Med Chem. 1999;42:2862-9 pubmed
    ..However, these compounds also demonstrated high affinities for sigma(1) and sigma(2) receptors and thus failed to show significantly improved selectivity over previously reported vesamicol analogues. ..
  45. Franke Radowiecka A. Vasoactive intestinal polypeptide (VIP)--immunoreactive nerve fibres in the mammary gland of the pig. Folia Morphol (Warsz). 2003;62:267-70 pubmed
    ..Less numerous VIP/SOM-IR fibres supplied the BV and were located around the LD of the gland. A small number of VIP-IR nerves also displayed immunoreactivity to NPY. VIP/NPY-IR nerve fibres supplied the BV of the gland. ..
  46. Park J, GONDRE LEWIS M, Eiden L, Loh Y. A distinct trans-Golgi network subcompartment for sorting of synaptic and granule proteins in neurons and neuroendocrine cells. J Cell Sci. 2011;124:735-44 pubmed publisher
    ..This specialized sorting compartment from which SPTVs and LDCVs bud might facilitate the acquisition of common exocytic machinery needed on the membranes of these vesicles. ..
  47. Dixon C, Kochanek P, Yan H, Schiding J, Griffith R, Baum E, et al. One-year study of spatial memory performance, brain morphology, and cholinergic markers after moderate controlled cortical impact in rats. J Neurotrauma. 1999;16:109-22 pubmed
    ..The inability of injured rats to benefit from repeated exposures to the MWM may represent a deficit in procedural memory that is independent of changes in hippocampal cholinergic systems. ..
  48. Lakomy M, Kaleczyc J, Wasowicz K, Czaja K. Immunohistochemical study of the otic ganglion in the pig. Pol J Vet Sci. 2002;5:257-62 pubmed
    ..ChAT- and VAChT-positive nerve fibers were numerous, while the number of nerve terminals containing NPY, VIP and SP was lower. GAL- and CGRP-positive nerve fibers were scarce. ..
  49. Malo M, Israel M. Expression of the acetylcholine release mechanism in various cells and reconstruction of the release mechanism in non-releasing cells. Life Sci. 2003;72:2029-38 pubmed
    ..A reconstruction of the release mechanism in cells particularly graftable cells, appears now possibly for ACh and probably for other transmitters. ..
  50. Bjur D, Danielson P, Alfredson H, Forsgren S. Presence of a non-neuronal cholinergic system and occurrence of up- and down-regulation in expression of M2 muscarinic acetylcholine receptors: new aspects of importance regarding Achilles tendon tendinosis (tendinopathy). Cell Tissue Res. 2008;331:385-400 pubmed
  51. Van der Zee E, Keijser J. Localization of pre- and postsynaptic cholinergic markers in rodent forebrain: a brief history and comparison of rat and mouse. Behav Brain Res. 2011;221:356-66 pubmed publisher
    ..This suggests a higher cholinergic tone in mouse than rat, and hence the animal model of choice may have consequences for cholinergic drug testing experiments. ..
  52. Golden J, Milbrandt J, Johnson E. Neurturin and persephin promote the survival of embryonic basal forebrain cholinergic neurons in vitro. Exp Neurol. 2003;184:447-55 pubmed
    ..Our results suggest that the GFLs may be effective as neuroprotective agents for BFCNs in vivo. ..
  53. Rafalzik S, Pehl U, Ott D, Strotmann J, Wolff M, Gerstberger R. Cholinergic signal transduction in the mouse sphenopalatine ganglion. Brain Res. 2008;1241:42-55 pubmed publisher
    ..Nicotinic signal transduction did not prove to be different in GFP-positive as compared to-negative murine SPG neurons. ..