Stimulation of vesicular monoamine transporter 2 activity by DJ-1 in SH-SY5Y cells

Biochemical and Biophysical Research Communications
Shizuma IshikawaSanae M M Iguchi-Ariga

Abstract

Loss-of-functional mutation in the DJ-1 gene causes a subset of familial Parkinson's disease. The mechanism underlying DJ-1-related selective vulnerability in the dopaminergic pathway is, however, not known. Dopamine is synthesized by two enzymes and then packed into synaptic vesicles by vesicular monoamine transporter 2 (VMAT2). In this study, we found that knockdown of DJ-1 expression reduced the levels of mRNA and protein of VMAT2, resulting in reduced VMAT2 activity. Co-immunoprecipitation and pull-down experiments revealed that DJ-1 directly bound to VMAT2, and DJ-1 was co-localized with VMAT2 in cells. Furthermore, ectopic expression of wild-type DJ-1, but not that of L166P, M26I and C106S mutants of DJ-1, increased mRNA and protein levels of VMAT2 and VMAT2 activity. Since VMAT2 and a portion of DJ-1 are localized in the synaptic membrane, these results suggest that DJ-1, but not pathogenically mutated DJ-1, stimulates VMAT2 activity in the synapse by transactivation of the VMAT gene and by direct binding to VMAT2 and that cysteine 106 is necessary for the stimulating activity of DJ-1 toward VMAT2.

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Jun 8, 2011·Neurobiology of Disease·Yukiko UsamiNobutaka Hattori

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Citations

Jun 15, 2013·Oxidative Medicine and Cellular Longevity·Hiroyoshi ArigaSanae M M Iguchi-Ariga
Apr 28, 2018·Cellular and Molecular Neurobiology·Amin Karimi-MoghadamMohammad Reza Jabalameli
Jun 2, 2015·Biological & Pharmaceutical Bulletin·Hiroyoshi Ariga
Nov 7, 2018·International Neurourology Journal·Wongyoung LeeSung Hyun Kim
Jul 12, 2020·Antioxidants·Kuo-Hsuan Chang, Chiung-Mei Chen

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