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

Published version
Peer-reviewed

Type

Article

Change log

Authors

van der Beek, Johannes Albertus 

Abstract

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.

Description

Keywords

Brownian dynamics simulations, SMLM, WASP, actin, clathrin, endocytosis, high-throughput, single-molecule localization microscopy, superresolution microscopy, Actin Cytoskeleton, Actins, Cell Membrane, Endocytosis, Microscopy, Fluorescence, Models, Theoretical, Protein Conformation, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Secretory Vesicles, Wiskott-Aldrich Syndrome Protein Family

Journal Title

Cell

Conference Name

Journal ISSN

0092-8674
1097-4172

Volume Title

174

Publisher

Elsevier BV