Vesicular acetylcholine transporter

The Vesicular acetylcholine transporter (VAChT) is a neurotransmitter transporter which is responsible for loading acetylcholine (ACh) into secretory organelles in neurons making acetylcholine available for secretion. It is encoded by Solute carrier family 18, member 3 (SLC18A3) gene, located within the first intron of the choline acetyltransferase gene. VAChT is able to transport ACh into vesicles by relying on an exchange between protons (H⁺) that were previously pumped into the vesicle diffusing out, thus acting as an antiporter. ACh molecules are then carried into the vesicle by the action of exiting protons. Acetylcholine transport utilizes a proton gradient established by a vacuolar ATPase.

SLC18A3
Identifiers
Aliases	SLC18A3, VACHT, solute carrier family 18 member A3, CMS21
External IDs	OMIM: 600336; MGI: 1101061; HomoloGene: 11022; GeneCards: SLC18A3; OMA:SLC18A3 - orthologs
Gene location (Human) Chr. Chromosome 10 (human) Band 10q11.23 Start 49,610,310 bp End 49,612,720 bp
Gene location (Mouse) Chr. Chromosome 14 (mouse) Band 14 B|14 19.4 cM Start 32,184,395 bp End 32,186,807 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gonad putamen caudate nucleus placenta muscle layer of sigmoid colon nucleus accumbens hypothalamus C1 segment muscle tissue pituitary gland Top expressed in lumbar subsegment of spinal cord facial motor nucleus anterior horn of spinal cord habenula neural tube embryo superior frontal gyrus basal plate embryo neural layer of retina More reference expression data BioGPS n/a
Gene ontology Molecular function acetylcholine binding acetylcholine transmembrane transporter activity Cellular component integral component of membrane plasma membrane clathrin-sculpted acetylcholine transport vesicle membrane AP-2 adaptor complex AP-1 adaptor complex clathrin-coated vesicle membrane presynapse membrane terminal bouton Biological process neurotransmitter transport neurotransmitter secretion transmembrane transport ammonium transmembrane transport membrane organization xenobiotic transmembrane transport organic cation transport acetate ester transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6572 20508 Ensembl ENSG00000187714 ENSMUSG00000100241 UniProt Q16572 O35304 Q3TYJ1 RefSeq (mRNA) NM_003055 NM_021712 RefSeq (protein) NP_003046 NP_068358 Location (UCSC) Chr 10: 49.61 – 49.61 Mb Chr 14: 32.18 – 32.19 Mb PubMed search
Wikidata
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VAChT uptake inhibitors

Radiolabeled compounds

PET imaging of the VAChT may provide insights into early diagnosis of Alzheimer's disease.

• (−)-trans-2-Hydroxy-3-(4-(4-[¹⁸F]fluorobenzoyl)piperidino)tetralin; racemate: Ki = 2.70 nM for VAChT, 191 nM for σ1, and 251 nM for σ2

Further reading

• Matsuo A, Bellier JP, Nishimura M, Yasuhara O, Saito N, Kimura H (Feb 2011). "Nuclear choline acetyltransferase activates transcription of a high-affinity choline transporter". The Journal of Biological Chemistry. 286 (7): 5836–45. doi:10.1074/jbc.M110.147611. PMC 3037696. PMID 21163949.
• Lau JK, Brown KC, Thornhill BA, Crabtree CM, Dom AM, Witte TR, Hardman WE, McNees CA, Stover CA, Carpenter AB, Luo H, Chen YC, Shiflett BS, Dasgupta P (Feb 2013). "Inhibition of cholinergic signaling causes apoptosis in human bronchioalveolar carcinoma". Cancer Research. 73 (4): 1328–39. doi:10.1158/0008-5472.CAN-12-3190. PMC 10461321. PMID 23222296.
• Varoqui H, Erickson JD (Nov 1996). "Active transport of acetylcholine by the human vesicular acetylcholine transporter". The Journal of Biological Chemistry. 271 (44): 27229–32. doi:10.1074/jbc.271.44.27229. PMID 8910293.
• Harold D, Peirce T, Moskvina V, Myers A, Jones S, Hollingworth P, Moore P, Lovestone S, Powell J, Foy C, Archer N, Walter S, Edmonson A, McIlroy S, Craig D, Passmore PA, Goate A, Hardy J, O'Donovan M, Williams J, Liddell M, Owen MJ, Jones L (Aug 2003). "Sequence variation in the CHAT locus shows no association with late-onset Alzheimer's disease". Human Genetics. 113 (3): 258–67. doi:10.1007/s00439-003-0960-2. PMID 12759818. S2CID 24977017.
• Morgan AR, Turic D, Jehu L, Hamilton G, Hollingworth P, Moskvina V, Jones L, Lovestone S, Brayne C, Rubinsztein DC, Lawlor B, Gill M, O'Donovan MC, Owen MJ, Williams J (Sep 2007). "Association studies of 23 positional/functional candidate genes on chromosome 10 in late-onset Alzheimer's disease". American Journal of Medical Genetics Part B. 144B (6): 762–70. doi:10.1002/ajmg.b.30509. PMID 17373700. S2CID 26081707.
• Schütz B, Chen L, Schäfer MK, Weihe E, Eiden LE (2000). "Somatomotor neuron-specific expression of the human cholinergic gene locus in transgenic mice". Neuroscience. 96 (4): 707–22. doi:10.1016/s0306-4522(99)00587-4. PMID 10727789. S2CID 44276305.
• Khare P, Mulakaluri A, Parsons SM (Nov 2010). "Search for the acetylcholine and vesamicol binding sites in vesicular acetylcholine transporter: the region around the lumenal end of the transport channel". Journal of Neurochemistry. 115 (4): 984–93. doi:10.1111/j.1471-4159.2010.06990.x. PMC 2962730. PMID 20831599.
• Tayebati SK, El-Assouad D, Ricci A, Amenta F (Nov 2002). "Immunochemical and immunocytochemical characterization of cholinergic markers in human peripheral blood lymphocytes". Journal of Neuroimmunology. 132 (1–2): 147–55. doi:10.1016/s0165-5728(02)00325-9. PMID 12417445. S2CID 20921312.
• Chireux MA, Le Van Thai A, Weber MJ (Mar 1995). "Human choline acetyltransferase gene: localization of alternative first exons". Journal of Neuroscience Research. 40 (4): 427–38. doi:10.1002/jnr.490400402. PMID 7616604. S2CID 42856768.

External links

• Vesicular+Acetylcholine+Transporter at the U.S. National Library of Medicine Medical Subject Headings (MeSH)