8thr

Structural highlights

Disease

VMAT2_HUMAN Brain dopamine-serotonin vesicular transport disease. The disease is caused by variants affecting the gene represented in this entry.

Function

VMAT2_HUMAN Electrogenic antiporter that exchanges one cationic monoamine with two intravesicular protons across the membrane of secretory and synaptic vesicles. Uses the electrochemical proton gradient established by the V-type proton-pump ATPase to accumulate high concentrations of monoamines inside the vesicles prior to their release via exocytosis. Transports a variety of catecholamines such as dopamine, adrenaline and noradrenaline, histamine, and indolamines such as serotonin (PubMed:8643547, PubMed:23363473). Regulates the transvesicular monoaminergic gradient that determines the quantal size. Mediates somatodendritic dopamine release in hippocampal neurons, likely as part of a regulated secretory pathway that integrates retrograde synaptic signals (By similarity). Acts as a primary transporter for striatal dopamine loading ensuring impulse-dependent release of dopamine at the synaptic cleft (By similarity). Responsible for histamine and serotonin storage and subsequent corelease from mast cell granules (PubMed:8860238) (By similarity).[UniProtKB:Q01827][UniProtKB:Q8BRU6]^{[1] [2] [3]}

References

1. ↑ Rilstone JJ, Alkhater RA, Minassian BA. Brain dopamine-serotonin vesicular transport disease and its treatment. N Engl J Med. 2013 Feb 7;368(6):543-50. PMID:23363473 doi:10.1056/NEJMoa1207281
2. ↑ Erickson JD, Schafer MK, Bonner TI, Eiden LE, Weihe E. Distinct pharmacological properties and distribution in neurons and endocrine cells of two isoforms of the human vesicular monoamine transporter. Proc Natl Acad Sci U S A. 1996 May 14;93(10):5166-71. PMID:8643547 doi:10.1073/pnas.93.10.5166
3. ↑ Erickson JD, Eiden LE, Schafer MK, Weihe E. Reserpine neuronal isoform of the vesicular monoamine transporter. J Mol Neurosci. 1995;6(4):277-87. PMID:8860238 doi:10.1007/BF02736786