Mechanistic Insights into Actin Force Generation During Vesicle Formation from Cryo-electron Tomography

Overview

Journal Dev Cell

Publisher Cell Press

Specialties Cell Biology
Reproductive Medicine

Date 2022 May 3

PMID 35504288

Authors

Daniel Serwas

Matthew Akamatsu

Amir Moayed

Karthik Vegesna

Ritvik Vasan

Jennifer M Hill

Johannes Schoneberg

Karen M Davies

Padmini Rangamani

David G Drubin

Affiliations

Soon will be listed here.

Abstract

Actin assembly provides force for a multitude of cellular processes. Compared to actin-assembly-based force production during cell migration, relatively little is understood about how actin assembly generates pulling forces for vesicle formation. Here, cryo-electron tomography identified actin filament number, organization, and orientation during clathrin-mediated endocytosis in human SK-MEL-2 cells, showing that force generation is robust despite variance in network organization. Actin dynamics simulations incorporating a measured branch angle indicate that sufficient force to drive membrane internalization is generated through polymerization and that assembly is triggered from ∼4 founding "mother" filaments, consistent with tomography data. Hip1R actin filament anchoring points are present along the entire endocytic invagination, where simulations show that it is key to pulling force generation, and along the neck, where it targets filament growth and makes internalization more robust. Actin organization described here allowed direct translation of structure to mechanism with broad implications for other actin-driven processes.

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