Editing Vesicular monoamine transporter (section)

==Genetic expression and transporter regulation==
Although both VMAT1 and VMAT2 are encoded by two different [[gene]]s, the individual genetic sequences demonstrate high homology. [[polymorphism (biology)|Polymorphism]]s in VMAT2 that affect regulation and quantitative [[Gene Expression|expression]] may pose genetic risk factors for PD. A specific VMAT1 gene (''SLC18A1'') has several associated [[polymorphism (biology)|polymorphism]]s, which have a [[locus (genetics)|locus]] 8p21.3 that has been strongly connected to [[schizophrenia]] susceptibility.<ref>{{Cite journal|last1=Lohoff|first1=Falk W.|last2=Weller|first2=Andrew E.|last3=Bloch|first3=Paul J.|last4=Buono|first4=Russell J.|last5=Doyle|first5=Glenn A.|last6=Ferraro|first6=Thomas N.|last7=Berrettini|first7=Wade H.|date=2008|title=Association between Polymorphisms in the Vesicular Monoamine Transporter 1 Gene (VMAT1/SLC18A1) on Chromosome 8p and Schizophrenia|journal=Neuropsychobiology|language=en|volume=57|issue=1–2|pages=55–60|doi=10.1159/000129668|issn=0302-282X|pmid=18451639|s2cid=39523023}}</ref>

Over-expression of VMAT2 results in increased secretion of neurotransmitter upon cell stimulation. Data suggests that deletion of the VMAT2 genes does not affect the size of small clear-core vesicles.

VMATs may be regulated by changes in [[transcription (genetics)|transcription]], post-transcriptional modifications such as [[phosphorylation]] and [[Mrna|mRNA]] [[RNA splicing|splicing]] of [[exons]], and vesicular transport inactivation facilitated by [[heterotrimeric G-proteins]], which are thought to be possessed by chromaffin granules, and have shown to regulate small clear-core vesicles.<ref name= "Fei"/><ref name="Brunk, I. 2006"/>

Specific heterotrimeric G-protein type regulation is tissue-dependent for VMAT2; it is not known whether this is the case for VMAT1. Heterotrimeric G-protein Gαo2 decreases VMAT1 activity in pancreatic and [[Adrenal medulla|adrenal medulla cells]], and activates heterotrimeric G-proteins to inhibit VMAT2 activity in the brain, regardless of whether they are localized on small clear-core or large-dense-core vesicles. The activated heterotrimeric G-protein Gαq downregulates VMAT2-mediated [[serotonin]] transport in blood platelets, but not in the brain, where Gαq completely inhibits VMAT2 activity.<ref name="Brunk, I. 2006"/> Although the exact signalling pathway for G-protein mediated regulation of VMATs is not known,<ref name="Brunk, I. 2006"/> it has recently been described that implicated G-proteins act directly on the VMATs.<ref>Remin, R., Schuldiner, S., 2003. Vesicular neurotransmitter transporters: Pharmacology, Biochemistry and Molecular Analysis. Neurotransmitter Transporters; Structure, Function, and Regulation, pp.313-354</ref>