TY - JOUR
T1 - Dimerization of Parkinson's disease-causing DJ-1 and formation of high molecular weight complexes in human brain
AU - Baulac, Stéphanie
AU - LaVoie, Matthew J.
AU - Strahle, Jennifer
AU - Schlossmacher, Michael G.
AU - Xia, Weiming
PY - 2004/11
Y1 - 2004/11
N2 - 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.
AB - 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.
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U2 - 10.1016/j.mcn.2004.06.014
DO - 10.1016/j.mcn.2004.06.014
M3 - Article
C2 - 15519239
AN - SCOPUS:7244229744
VL - 27
SP - 236
EP - 246
JO - Molecular and Cellular Neuroscience
JF - Molecular and Cellular Neuroscience
SN - 1044-7431
IS - 3
ER -