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

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Title: Stimulation of vesicular monoamine transporter 2 activity by DJ-1 in SH-SY5Y cells
Authors: Ishikawa, Shizuma Browse this author
Tanaka, Yuki Browse this author
Takahashi-Niki, Kazuko Browse this author →KAKEN DB
Niki, Takeshi Browse this author →KAKEN DB
Ariga, Hiroyoshi Browse this author →KAKEN DB
Iguchi-Ariga, Sanae M. M. Browse this author →KAKEN DB
Keywords: DJ-1
Issue Date: 18-May-2012
Publisher: Elsevier
Journal Title: Biochemical and Biophysical Research Communications
Volume: 421
Issue: 4
Start Page: 813
End Page: 818
Publisher DOI: 10.1016/j.bbrc.2012.04.095
PMID: 22554508
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, M261 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.
Type: article (author version)
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 有賀 寛芳

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