Pfitzner, Anna-Katharina; Mercier, Vincent; Jiang, Xiuyun; Moser von Filseck, Joachim; Baum, Buzz; Šarić, AnđelaISTA ; Roux, Aurélien
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.
The authors thank Nicolas Chiaruttini, Jean Gruenberg, and Lena Harker-Kirschneck for careful correction of this manuscript and helpful discussions. The authors want to thank the NCCR Chemical Biology for constant support during this project. A.R. acknowledges funding from the Swiss National Fund for Research (31003A_130520, 31003A_149975, and 31003A_173087) and the European Research Council Consolidator (311536). A.Š. acknowledges the European Research Council (802960). B.B. thanks the BBSRC (BB/K009001/1) and Wellcome Trust (203276/Z/16/Z) for support. J.M.v.F. acknowledges funding through an EMBO Long-Term Fellowship (ALTF 1065-2015), the European Commission FP7 (Marie Curie Actions, LTFCOFUND2013, and GA-2013-609409), and a Transitional Postdoc fellowship (2015/345) from the Swiss SystemsX.ch initiative, evaluated by the Swiss National Science Foundation and Swiss National Science Foundation Research (SNSF SINERGIA 160728/1 [leader, Sophie Martin]).
Pfitzner A-K, Mercier V, Jiang X, et al. An ESCRT-III polymerization sequence drives membrane deformation and fission. Cell. 2020;182(5):1140-1155.e18. doi:10.1016/j.cell.2020.07.021
Pfitzner, A.-K., Mercier, V., Jiang, X., Moser von Filseck, J., Baum, B., Šarić, A., & Roux, A. (2020). An ESCRT-III polymerization sequence drives membrane deformation and fission. Cell. Elsevier. https://doi.org/10.1016/j.cell.2020.07.021
Pfitzner, Anna-Katharina, Vincent Mercier, Xiuyun Jiang, Joachim Moser von Filseck, Buzz Baum, Anđela Šarić, and Aurélien Roux. “An ESCRT-III Polymerization Sequence Drives Membrane Deformation and Fission.” Cell. Elsevier, 2020. https://doi.org/10.1016/j.cell.2020.07.021.
A.-K. Pfitzner et al., “An ESCRT-III polymerization sequence drives membrane deformation and fission,” Cell, vol. 182, no. 5. Elsevier, p. 1140–1155.e18, 2020.
Pfitzner A-K, Mercier V, Jiang X, Moser von Filseck J, Baum B, Šarić A, Roux A. 2020. An ESCRT-III polymerization sequence drives membrane deformation and fission. Cell. 182(5), 1140–1155.e18.
Pfitzner, Anna-Katharina, et al. “An ESCRT-III Polymerization Sequence Drives Membrane Deformation and Fission.” Cell, vol. 182, no. 5, Elsevier, 2020, p. 1140–1155.e18, doi:10.1016/j.cell.2020.07.021.
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