Rab-alphaGDI activity is regulated by a Hsp90 chaperone complex.
The Rab-specific alphaGDP-dissociation inhibitor (alphaGDI) regulates the recycling of Rab GTPases. We have now identified a novel alphaGDI complex from synaptic membranes that contains three chaperone components: Hsp90, Hsc70 and cysteine string protein (CSP). We find that the alphaGDI-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 alphaGDI to recycle Rab3A during neurotransmitter release. We propose that alphaGDI 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.
Sakisaka
Toshiaki
T
Departments of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Meerlo
Timo
T
Matteson
Jeanne
J
Plutner
Helen
H
Balch
William E
WE
D000255:Adenosine Triphosphate / Q000502:physiology; D020816:Amino Acid Motifs; D000818:Animals; D016227:Benzoquinones; D001921:Brain / Q000166:cytology; D020013:Calcium Signaling; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000737:chemistry / Q000502:physiology*; D050883:HSC70 Heat-Shock Proteins; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D047029:Lactams, Macrocyclic; D007783:Lactones / Q000494:pharmacology; D018942:Macrolides; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000502:physiology*; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D017510:Protein Folding; D011809:Quinones / Q000494:pharmacology; D051381:Rats; D013574:Synaptosomes / Q000378:metabolism*; D020761:rab1 GTP-Binding Proteins / Q000378:metabolism; D020692:rab3 GTP-Binding Proteins / Q000378:metabolism
D016227:Benzoquinones; C086796:GDP dissociation inhibitor 1; D020730:Guanine Nucleotide Dissociation Inhibitors; D050883:HSC70 Heat-Shock Proteins; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; C494373:Hspa8 protein, rat; D047029:Lactams, Macrocyclic; D007783:Lactones; D018942:Macrolides; D046911:Macromolecular Substances; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D011809:Quinones; C088460:cysteine string protein; D000255:Adenosine Triphosphate; D020761:rab1 GTP-Binding Proteins; D020692:rab3 GTP-Binding Proteins; C035359:monorden; C001277:geldanamycin