Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA; email:
Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158, USA.
Annu Rev Cell Dev Biol. 2018 Oct 6;34:85-109. doi: 10.1146/annurev-cellbio-100616-060600. Epub 2018 Aug 10.
The endosomal sorting complexes required for transport (ESCRT) pathway mediates cellular membrane remodeling and fission reactions. The pathway comprises five core complexes: ALIX, ESCRT-I, ESCRT-II, ESCRT-III, and Vps4. These soluble complexes are typically recruited to target membranes by site-specific adaptors that bind one or both of the early-acting ESCRT factors: ALIX and ESCRT-I/ESCRT-II. These factors, in turn, nucleate assembly of ESCRT-III subunits into membrane-bound filaments that recruit the AAA ATPase Vps4. Together, ESCRT-III filaments and Vps4 remodel and sever membranes. Here, we review recent advances in our understanding of the structures, activities, and mechanisms of the ESCRT-III and Vps4 machinery, including the first high-resolution structures of ESCRT-III filaments, the assembled Vps4 enzyme in complex with an ESCRT-III substrate, the discovery that ESCRT-III/Vps4 complexes can promote both inside-out and outside-in membrane fission reactions, and emerging mechanistic models for ESCRT-mediated membrane fission.
内体分选复合物需要运输（ESCRT）途径介导细胞的膜重塑和裂变反应。该途径包括五个核心复合物：ALIX、ESCRT-I、ESCRT-II、ESCRT-III 和 Vps4。这些可溶性复合物通常通过特异性结合早期 ESCRT 因子之一或两者的衔接蛋白募集到靶膜：ALIX 和 ESCRT-I/ESCRT-II。反过来，这些因子核化 ESCRT-III 亚基组装成膜结合的纤维，招募 AAA ATPase Vps4。ESCRT-III 纤维和 Vps4 一起重塑和切断膜。在这里，我们回顾了对 ESCRT-III 和 Vps4 机制的结构、活性和机制的最新理解进展，包括 ESCRT-III 纤维的第一个高分辨率结构、组装的 Vps4 酶与 ESCRT-III 底物的复合物、发现 ESCRT-III/Vps4 复合物可以促进内翻和外翻的膜裂变反应，以及新兴的 ESCRT 介导的膜裂变机制模型。
