An ESCRT-III Polymerization Sequence Drives Membrane Deformation and Fission

Anna-Katharina Pfitzner; Vincent Mercier; Xiuyun Jiang; Joachim Moser von Filseck; Buzz Baum; Anđela Šarić; Aurélien Roux

doi:10.1016/j.cell.2020.07.021

An ESCRT-III Polymerization Sequence Drives Membrane Deformation and Fission

Cell. 2020 Sep 3;182(5):1140-1155.e18. doi: 10.1016/j.cell.2020.07.021. Epub 2020 Aug 18.

Authors

Anna-Katharina Pfitzner¹, Vincent Mercier², Xiuyun Jiang³, Joachim Moser von Filseck¹, Buzz Baum⁴, Anđela Šarić³, Aurélien Roux⁵

Affiliations

¹ Department of Biochemistry, University of Geneva, 1211 Geneva, Switzerland.
² Department of Biochemistry, University of Geneva, 1211 Geneva, Switzerland; National Center of Competence in Research in Chemical Biology, University of Geneva, 1211 Geneva, Switzerland.
³ Department of Physics and Astronomy, University College London, Gower Street, London WC1E 6BT, UK; Institute for the Physics of Living Systems, University College London, Gower Street, London WC1E 6BT, UK; MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK.
⁴ Institute for the Physics of Living Systems, University College London, Gower Street, London WC1E 6BT, UK; MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK.
⁵ Department of Biochemistry, University of Geneva, 1211 Geneva, Switzerland; National Center of Competence in Research in Chemical Biology, University of Geneva, 1211 Geneva, Switzerland. Electronic address: aurelien.roux@unige.ch.

Abstract

The endosomal sorting complex required for transport-III (ESCRT-III) catalyzes membrane fission from within membrane necks, a process that is essential for many cellular functions, from cell division to lysosome degradation and autophagy. How it breaks membranes, though, remains unknown. Here, we characterize a sequential polymerization of ESCRT-III subunits that, driven by a recruitment cascade and by continuous subunit-turnover powered by the ATPase Vps4, induces membrane deformation and fission. During this process, the exchange of Vps24 for Did2 induces a tilt in the polymer-membrane interface, which triggers transition from flat spiral polymers to helical filament to drive the formation of membrane protrusions, and ends with the formation of a highly constricted Did2-Ist1 co-polymer that we show is competent to promote fission when bound on the inside of membrane necks. Overall, our results suggest a mechanism of stepwise changes in ESCRT-III filament structure and mechanical properties via exchange of the filament subunits to catalyze ESCRT-III activity.

Keywords: CHMP1; CHMP4; Did2; ESCRT; ESCRT-III; Ist1; Snf7; Vps2; in vitro reconstitution; membrane fission; membrane remodeling.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphatases / metabolism
Cell Line, Tumor
Cell Membrane / metabolism*
Endosomal Sorting Complexes Required for Transport / metabolism*
Endosomes / metabolism
HeLa Cells
Humans
Membrane Fusion / physiology*
Polymerization
Protein Transport / physiology

Substances

Endosomal Sorting Complexes Required for Transport
Adenosine Triphosphatases

Abstract

Publication types

MeSH terms

Substances

Grants and funding