A novel HSP90 chaperone complex regulates intracellular vesicle transport.
Heat shock protein 90 (HSP90) is considered a specialized molecular chaperone that controls the folding of cell-regulatory proteins such as steroid receptors and kinases. However, its high abundance is suggestive of a more general function in other fundamental processes. Here, we show that HSP90 is required for vesicular protein transport in the cell. We have identified a novel chaperone complex comprising HSP90 and TPR1 that is recruited to the membrane protein VAP-33. Depletion of the TPR1 protein in mammalian cells inhibits transport of vesicular stomatitis virus glycoprotein (VSVG) and leads to accumulation of this cargo protein in the Golgi apparatus. Furthermore, trafficking of VSVG between Golgi stacks is dependent on the ATPase function of HSP90 and can be inhibited by drugs specific for HSP90. Our results identify a new role for HSP90 in protein sorting, pointing to a central role for this molecular chaperone in the cell.
Lotz
Gregor P
GP
Protein Folding Group, Institute for Genetics, University of Bonn, Römerstr. 164, 53117 Bonn, Germany.
Brychzy
Alexander
A
Heinz
Stefan
S
Obermann
Wolfgang M J
WM
D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D004705:Endocytosis / Q000502:physiology; D006056:Golgi Apparatus / Q000378:metabolism / Q000648:ultrastructure; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism*; D046911:Macromolecular Substances / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D022161:Transport Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D033921:Vesicular Transport Proteins / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism
D033942:Adaptor Proteins, Vesicular Transport; D018841:HSP90 Heat-Shock Proteins; D046911:Macromolecular Substances; D018832:Molecular Chaperones; C475144:TTC1 protein, human; C114051:VAPA protein, human; D033921:Vesicular Transport Proteins; D014764:Viral Proteins; D000251:Adenosine Triphosphatases; D020962:Heterotrimeric GTP-Binding Proteins