瑞士日内瓦大学Aurélien Roux研究组发现，ESCRT-III的聚合顺序可驱动膜变形和裂变。该项研究成果于2020年8月18日在线发表在《细胞》杂志上。

研究人员表征了由募集级联和ATPase Vps4支持的连续亚基转换所驱动的转运所需内吞体分选复合物-III（ESCRT-III）亚基的依次聚合、诱导膜变形和裂变。在此过程中，Vps24与Did2的交换会引起聚合物-膜界面的倾斜，从而触发从扁平螺旋聚合物到螺旋丝的过渡，进而驱动膜突起的形成，并最终形成高度收缩的Did2-Ist1共聚物，研究人员发现这一组分结合在膜颈内部时能够促进裂变。

总体而言，这些结果揭示了ESCRT-III细丝结构和机械性能的逐步变化的，其通过交换细丝亚基来催化ESCRT-III活性。

据介绍，ESCRT-III催化膜颈内部的膜裂变，这是许多细胞功能必不可少的过程，包括从细胞分裂到溶酶体降解和自噬。然而，如何破膜仍然未知。

附：英文原文

Title: An ESCRT-III Polymerization Sequence Drives Membrane Deformation and Fission

Author: Anna-Katharina Pfitzner, Vincent Mercier, Xiuyun Jiang, Joachim Moser von Filseck, Buzz Baum, Anela ari, Aurélien Roux

Issue&Volume: 2020-08-18

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.

DOI: 10.1016/j.cell.2020.07.021

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30929-6