Dimerization of Parkinson's disease-causing DJ-1 and formation of high molecular weight complexes in human brain

Stéphanie Baulac, Matthew J. LaVoie, Jennifer Strahle, Michael G. Schlossmacher, Weiming Xia

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Mutations in the DJ-1 gene have been implicated in the PARK7-linked autosomal recessive form of Parkinson's disease (PD). The molecular properties of DJ-1 WT, DJ-1 L166P, and a newly identified disease-causing mutant DJ-1 M26I were explored after they were transiently expressed in mammalian cells. Treatment of intact, living cells with the chemical crosslinker disuccinimidyl suberate (DSS) revealed that DJ-1 WT and mutant DJ-1 M26I were present as stable homodimers; DJ-1 L166P in particular tended to form high-order complexes as well. In contrast to DJ-1 L166P that is quickly degraded by the proteasome, DJ-1 M26I was found to be an efficiently expressed and stable variant of DJ-1, suggesting that these mutations have distinct biochemical effects on DJ-1. We further provide evidence that in human brain, under nondenaturing conditions, DJ-1 is present in high molecular weight (HMW) complexes of approximately 250-700 kDa containing parkin, another PD-associated protein.

Original languageEnglish (US)
Pages (from-to)236-246
Number of pages11
JournalMolecular and Cellular Neuroscience
Volume27
Issue number3
DOIs
StatePublished - Nov 2004

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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