RRC ID 57170
Author Lauwers E, Wang YC, Gallardo R, Van der Kant R, Michiels E, Swerts J, Baatsen P, Zaiter SS, McAlpine SR, Gounko NV, Rousseau F, Schymkowitz J, Verstreken P.
Title Hsp90 Mediates Membrane Deformation and Exosome Release.
Journal Mol Cell
Abstract Hsp90 is an essential chaperone that guards proteome integrity and amounts to 2% of cellular protein. We now find that Hsp90 also has the ability to directly interact with and deform membranes via an evolutionarily conserved amphipathic helix. Using a new cell-free system and in vivo measurements, we show this amphipathic helix allows exosome release by promoting the fusion of multivesicular bodies (MVBs) with the plasma membrane. We dissect the relationship between Hsp90 conformation and membrane-deforming function and show that mutations and drugs that stabilize the open Hsp90 dimer expose the helix and allow MVB fusion, while these effects are blocked by the closed state. Hence, we structurally separated the Hsp90 membrane-deforming function from its well-characterized chaperone activity, and we show that this previously unrecognized function is required for exosome release.
Volume 71(5)
Pages 689-702.e9
Published 2018-9-6
DOI 10.1016/j.molcel.2018.07.016
PII S1097-2765(18)30585-9
PMID 30193096
MeSH Animals Cell Membrane / metabolism* Cell-Free System / metabolism Drosophila / metabolism Exosomes / metabolism* Female HSP90 Heat-Shock Proteins / metabolism* Male Molecular Chaperones / metabolism Multivesicular Bodies / metabolism Protein Binding / physiology Protein Conformation
IF 14.548
Times Cited 18