Systematic Nanoscale Analysis of Endocytosis Links Efficient Vesicle Formation to Patterned Actin Nucleation

被引：137

作者：

Mund, Markus ^{[1
]}

van der Beek, Johannes Albertus ^{[1
]}

Deschamps, Joran ^{[1
]}

Dmitrieff, Serge ^{[1
,5
]}

Hoess, Philipp ^{[1
,4
]}

Monster, Jooske Louise ^{[1
]}

Picco, Andrea ^{[2
,3
]}

Nedelec, Francois ^{[1
]}

Kaksonen, Marko ^{[2
,3
]}

Ries, Jonas ^{[1
]}

机构：

[1] EMBL, Cell Biol & Biophys Unit, Meyerhofstr 1, D-69117 Heidelberg, Germany

[2] Univ Geneva, Dept Biochem, Quai Ernest Ansermet 30, CH-1211 Geneva, Switzerland

[3] Univ Geneva, NCCR Chem Biol, Quai Ernest Ansermet 30, CH-1211 Geneva, Switzerland

[4] EMBL & Heidelberg Univ, Fac Biosci, Heidelberg, Germany

[5] Inst Jacques Monod, 15 Rue Helene Brion, F-75013 Paris, France

来源：

CELL | 2018年 / 174卷 / 04期

基金：

瑞士国家科学基金会; 欧洲研究理事会;

关键词：

CLATHRIN-MEDIATED ENDOCYTOSIS; SINGLE-MOLECULE LOCALIZATION; FISSION YEAST; PLASMA-MEMBRANE; FLUORESCENT PROTEINS; ARP2/3; COMPLEX; BUDDING YEAST; MICROSCOPY; CYTOSKELETON; DYNAMICS;

D O I：

10.1016/j.cell.2018.06.032

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Clathrin-mediated endocytosis is an essential cellular function in all eukaryotes that is driven by a self-assembled macromolecular machine of over 50 different proteins in tens to hundreds of copies. How these proteins are organized to produce endocytic vesicles with high precision and efficiency is not understood. Here, we developed high-throughput superresolution microscopy to reconstruct the nanoscale structural organization of 23 endocytic proteins from over 100,000 endocytic sites in yeast. We found that proteins assemble by radially ordered recruitment according to function. WASP family proteins form a circular nanoscale template on the membrane to spatially control actin nucleation during vesicle formation. Mathematical modeling of actin polymerization showed that this WASP nano-template optimizes force generation for membrane invagination and substantially increases the efficiency of endocytosis. Such nanoscale pre-patterning of actin nucleation may represent a general design principle for directional force generation in membrane remodeling processes such as during cell migration and division.

引用

页码：884 / +

页数：30

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