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Stimulation of vesicular monoamine transporter 2 activity by DJ-1 in SH-SY5Y cells
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 | VMAT2 | Dopamine |
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) |
URI: | http://hdl.handle.net/2115/49554 |
Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 有賀 寛芳
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