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Title
  • en Stimulation of vesicular monoamine transporter 2 activity by DJ-1 in SH-SY5Y cells
Creator
Accessrights open access
Subject
  • Other en DJ-1
  • Other en VMAT2
  • Other en Dopamine
  • NDC 464
Description
  • Abstract en 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.
Publisher en Elsevier
Date
    Issued2012-05-18
Language
  • eng
Resource Type journal article
Version Type AM
Identifier HDL http://hdl.handle.net/2115/49554
Relation
  • isVersionOf DOI https://doi.org/10.1016/j.bbrc.2012.04.095
  • PMID 22554508
Journal
    • PISSN 0006-291X
      • en Biochemical and Biophysical Research Communications
      • Volume Number421 Issue Number4 Page Start813 Page End818
File
Oaidate 2023-07-26