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

Ishikawa, Shizuma

Tanaka, Yuki

Takahashi-Niki, Kazuko

Niki, Takeshi

Ariga, Hiroyoshi

Iguchi-Ariga, Sanae M. M.

Subject
  • Other DJ-1
  • Other VMAT2
  • Other Dopamine
  • NDC 464
Description
Other
  • 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.
PublisherElsevier
Date Issued 2012-05-18
Languageeng
NIItypejournal article
VersiontypeAM
Identifier URI http://hdl.handle.net/2115/49554
Relation
  • isIdenticalTo PMID 22554508
  • isIdenticalTo DOI https://doi.org/10.1016/j.bbrc.2012.04.095
Journal
    • ISSN 0006-291X
    • Biochemical and Biophysical Research Communications
    421(4), 813-818
File
Oaidate2019-03-15T05:20:36Z