BAG1 restores formation of functional DJ-1 L166P dimers and DJ-1 chaperone activity.
Mutations in the gene coding for DJ-1 protein lead to early-onset recessive forms of Parkinson's disease. It is believed that loss of DJ-1 function is causative for disease, although the function of DJ-1 still remains a matter of controversy. We show that DJ-1 is localized in the cytosol and is ... associated with membranes and organelles in the form of homodimers. The disease-related mutation L166P shifts its subcellular distribution to the nucleus and decreases its ability to dimerize, impairing cell survival. Using an intracellular foldase biosensor, we found that wild-type DJ-1 possesses chaperone activity, which is abolished by the L166P mutation. We observed that this aberrant phenotype can be reversed by the expression of the cochaperone BAG1 (Bcl-2-associated athanogene 1), restoring DJ-1 subcellular distribution, dimer formation, and chaperone activity and ameliorating cell survival.
Mesh Terms:
Amino Acid Substitution, Cell Death, Cell Line, DNA-Binding Proteins, Humans, Immunoprecipitation, Intracellular Signaling Peptides and Proteins, Molecular Chaperones, Mutant Proteins, Oncogene Proteins, Protein Binding, Protein Multimerization, Protein Transport, Recombinant Proteins, Subcellular Fractions, Transcription Factors
Amino Acid Substitution, Cell Death, Cell Line, DNA-Binding Proteins, Humans, Immunoprecipitation, Intracellular Signaling Peptides and Proteins, Molecular Chaperones, Mutant Proteins, Oncogene Proteins, Protein Binding, Protein Multimerization, Protein Transport, Recombinant Proteins, Subcellular Fractions, Transcription Factors
J. Cell Biol.
Date: Feb. 22, 2010
PubMed ID: 20156966
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