Hsp90 Mediates Membrane Deformation and Exosome Release.

Autor:	Lauwers E; VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; KU Leuven, Department of Neurosciences, Leuven Brain Institute, 3000 Leuven, Belgium. Electronic address: elsa.lauwers@kuleuven.vib.be., Wang YC; VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; KU Leuven, Department of Neurosciences, Leuven Brain Institute, 3000 Leuven, Belgium., Gallardo R; VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; KU Leuven, SWITCH lab, Department of Cellular and Molecular Medicine, 3000 Leuven, Belgium., Van der Kant R; VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; KU Leuven, SWITCH lab, Department of Cellular and Molecular Medicine, 3000 Leuven, Belgium., Michiels E; VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; KU Leuven, SWITCH lab, Department of Cellular and Molecular Medicine, 3000 Leuven, Belgium., Swerts J; VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; KU Leuven, Department of Neurosciences, Leuven Brain Institute, 3000 Leuven, Belgium., Baatsen P; VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; KU Leuven, Department of Neurosciences, Leuven Brain Institute, 3000 Leuven, Belgium; Electron Microscopy Expertise Unit and VIB Bio Imaging Core, 3000 Leuven, Belgium., Zaiter SS; School of Chemistry, University of New South Wales, Sydney, NSW 2051, Australia., McAlpine SR; School of Chemistry, University of New South Wales, Sydney, NSW 2051, Australia., Gounko NV; VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; KU Leuven, Department of Neurosciences, Leuven Brain Institute, 3000 Leuven, Belgium; Electron Microscopy Expertise Unit and VIB Bio Imaging Core, 3000 Leuven, Belgium., Rousseau F; VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; KU Leuven, SWITCH lab, Department of Cellular and Molecular Medicine, 3000 Leuven, Belgium., Schymkowitz J; VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; KU Leuven, SWITCH lab, Department of Cellular and Molecular Medicine, 3000 Leuven, Belgium., Verstreken P; VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; KU Leuven, Department of Neurosciences, Leuven Brain Institute, 3000 Leuven, Belgium. Electronic address: patrik.verstreken@kuleuven.vib.be.
Jazyk:	angličtina
Zdroj:	Molecular cell [Mol Cell] 2018 Sep 06; Vol. 71 (5), pp. 689-702.e9.
DOI:	10.1016/j.molcel.2018.07.016
Abstrakt:	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. (Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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