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