Hsp90 mediates membrane deformation and exosome release

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 this is 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.


Elsa Lauwers (1, 2)
Yu-Chung Wang (1, 2)
Rob Van der Kant (1, 3)
Emiel Michiels (1, 3)
Jef Swerts (1, 2)
Pieter Baatsen (1, 2, 4)
Rodrigo Gallardo (1, 3)
Natalia V. Gounko (1, 2, 4)
Frederic Rousseau (1, 3)
Joost Schymkowitz (1, 3)
Patrik Verstreken (1, 2)


VIB-KU Leuven Center for Brain & Disease Research(1)
KU Leuven Department of Neurosciences (2)
KU Leuven SWITCH lab Department of Cellular and Molecular Medicine (3)
Electron Microscopy Expertise unit & VIB Bio Imaging Core 3000 Leuven, Belgium (4)

Presenting author

Yu-Chun Wang, PhD student, VIB-KU Leuven Center for Brain & Disease Research, KU Leuven, Department of Neurosciences
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