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An ESCRT-III Polymerization Sequence Drives Membrane Deformation and Fission

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 ch...

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Autores principales: Pfitzner, Anna-Katharina, Mercier, Vincent, Jiang, Xiuyun, Moser von Filseck, Joachim, Baum, Buzz, Šarić, Anđela, Roux, Aurélien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479521/
https://www.ncbi.nlm.nih.gov/pubmed/32814015
http://dx.doi.org/10.1016/j.cell.2020.07.021
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author Pfitzner, Anna-Katharina
Mercier, Vincent
Jiang, Xiuyun
Moser von Filseck, Joachim
Baum, Buzz
Šarić, Anđela
Roux, Aurélien
author_facet Pfitzner, Anna-Katharina
Mercier, Vincent
Jiang, Xiuyun
Moser von Filseck, Joachim
Baum, Buzz
Šarić, Anđela
Roux, Aurélien
author_sort Pfitzner, Anna-Katharina
collection PubMed
description 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.
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spelling pubmed-74795212020-09-16 An ESCRT-III Polymerization Sequence Drives Membrane Deformation and Fission Pfitzner, Anna-Katharina Mercier, Vincent Jiang, Xiuyun Moser von Filseck, Joachim Baum, Buzz Šarić, Anđela Roux, Aurélien Cell Article 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. Cell Press 2020-09-03 /pmc/articles/PMC7479521/ /pubmed/32814015 http://dx.doi.org/10.1016/j.cell.2020.07.021 Text en Crown Copyright © 2020 Published by Elsevier Inc. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Pfitzner, Anna-Katharina
Mercier, Vincent
Jiang, Xiuyun
Moser von Filseck, Joachim
Baum, Buzz
Šarić, Anđela
Roux, Aurélien
An ESCRT-III Polymerization Sequence Drives Membrane Deformation and Fission
title An ESCRT-III Polymerization Sequence Drives Membrane Deformation and Fission
title_full An ESCRT-III Polymerization Sequence Drives Membrane Deformation and Fission
title_fullStr An ESCRT-III Polymerization Sequence Drives Membrane Deformation and Fission
title_full_unstemmed An ESCRT-III Polymerization Sequence Drives Membrane Deformation and Fission
title_short An ESCRT-III Polymerization Sequence Drives Membrane Deformation and Fission
title_sort escrt-iii polymerization sequence drives membrane deformation and fission
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479521/
https://www.ncbi.nlm.nih.gov/pubmed/32814015
http://dx.doi.org/10.1016/j.cell.2020.07.021
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