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Principles of self-organization and load adaptation by the actin cytoskeleton during clathrin-mediated endocytosis

TitlePrinciples of self-organization and load adaptation by the actin cytoskeleton during clathrin-mediated endocytosis
Publication TypeJournal Article
Year of Publication2020
AuthorsAkamatsu M, Vasan R, Serwas D, Ferrin MA, Rangamani P, Drubin DG
JournaleLife
Volume9
Abstract

Force generation by actin assembly shapes cellular membranes. An experimentally constrained multiscale model shows that a minimal branched actin network is sufficient to internalize endocytic pits against membrane tension. Around 200 activated Arp2/3 complexes are required for robust internalization. A newly developed molecule-counting method determined that ~200 Arp2/3 complexes assemble at sites of clathrin-mediated endocytosis in human cells. Simulations predict that actin self-organizes into a radial branched array with growing ends oriented toward the base of the pit. Long actin filaments bend between attachment sites in the coat and the base of the pit. Elastic energy stored in bent filaments, whose presence was confirmed by cryo-electron tomography, contributes to endocytic internalization. Elevated membrane tension directs more growing filaments toward the base of the pit, increasing actin nucleation and bending for increased force production. Thus, spatially constrained actin filament assembly utilizes an adaptive mechanism enabling endocytosis under varying physical constraints.

 
DOI10.7554/elife.49840
Fields of interest: