Stimulation of vesicular monoamine transporter 2 activity by DJ-1 in SH-SY5Y cells.
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.
Mesh Terms:
Cell Line, Cysteine, Gene Knockdown Techniques, Humans, Immunoprecipitation, Intracellular Signaling Peptides and Proteins, Mutation, Oncogene Proteins, Parkinson Disease, RNA, Small Interfering, Synapses, Transcriptional Activation, Vesicular Monoamine Transport Proteins
Cell Line, Cysteine, Gene Knockdown Techniques, Humans, Immunoprecipitation, Intracellular Signaling Peptides and Proteins, Mutation, Oncogene Proteins, Parkinson Disease, RNA, Small Interfering, Synapses, Transcriptional Activation, Vesicular Monoamine Transport Proteins
Biochem. Biophys. Res. Commun.
Date: May. 18, 2012
PubMed ID: 22554508
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