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  • The EMBO Journal (2002) 21, 6125 - 6135
  • doi:10.1093/emboj/cdf603

Rab-alphaGDI activity is regulated by a Hsp90 chaperone complex

Toshiaki Sakisaka1, Timo Meerlo2, Jeanne Matteson1, Helen Plutner1 and William E. Balch1,3

  1. Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
  2. Department of Cellular and Molecular Medicine, University of California, San Diego, School of Medicine, La Jolla, CA 92093, USA
  3. Institute for Childhood and Neglected Diseases, The Scripps Research Institute, La Jolla, CA 92037, USA

Correspondence to:

William E. Balch, E-mail: webalch@scripps.edu

Received 2 August 2002; Accepted 23 September 2002; Revised 17 September 2002

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 Ca2+-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 Ca2+-dependent events triggering Rab-GTP hydrolysis with retrieval of Rab-GDP to the cytosol.

  • Keywords:

    • CSP,
    • GDI,
    • Hsp90,
    • Rab3A,
    • synaptic vesicle