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Rab‐αGDI activity is regulated by a Hsp90 chaperone complex
Author(s) -
Sakisaka Toshiaki,
Meerlo Timo,
Matteson Jeanne,
Plutner Helen,
Balch William E.
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdf603
Subject(s) - rab , biology , chaperone (clinical) , hsp90 , gtpase , microbiology and biotechnology , cytosol , biochemistry , heat shock protein , enzyme , gene , medicine , pathology
The Rab‐specific αGDP‐dissociation inhibitor (αGDI) regulates the recycling of Rab GTPases. We have now identified a novel αGDI complex from synaptic membranes that contains three chaperone components: Hsp90, Hsc70 and cysteine string protein (CSP). We find that the αGDI–chaperone complex is dissociated in response to Ca 2+ ‐induced neurotransmitter release, that chaperone complex dissociation is sensitive to the Hsp90 inhibitor geldanamycin (GA) and that GA inhibits the ability of αGDI to recycle Rab3A during neurotransmitter release. We propose that αGDI interacts with a specialized membrane‐associated Rab recycling Hsp90 chaperone system on the vesicle membrane to coordinate the Ca 2+ ‐dependent events triggering Rab‐GTP hydrolysis with retrieval of Rab‐GDP to the cytosol.