Use of Hsp90 inhibitors to disrupt GDI-dependent Rab recycling.
Guanine nucleotide dissociation inhibitor (GDI) is a central regulator of Rab GTPase family members. GDI recycles Rab proteins from the membrane and sequesters the inactive GDP-bound form of Rab in the cytosol for use in multiple rounds of transport. The balance between the membrane-bound form of Rab and the cytosolic reserve pool of the Rab-GDI complex is critical for vesicular trafficking between membrane compartments. Recycling of Rab GTPases is likely to require a membrane-bound complex of GDI, Hsp90, and Rab given that alphaGDI-dependent recycling of Rab3A at the synapse and neurotransmitter transmitter release is inhibited by Hsp90-specific inhibitors. Here we describe methods required for establishing the dependence of Rab recycling pathways on Hsp90 in vitro.
Chen
Christine Y
CY
Sakisaka
Toshiaki
T
Balch
William E
WE
D000818:Animals; D002478:Cells, Cultured; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism; D020692:rab3 GTP-Binding Proteins / Q000378:metabolism*
D020730:Guanine Nucleotide Dissociation Inhibitors; D018841:HSP90 Heat-Shock Proteins; D011994:Recombinant Proteins; D020692:rab3 GTP-Binding Proteins