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

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...

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Detalles Bibliográficos
Autores principales: Akamatsu, Matthew, Vasan, Ritvik, Serwas, Daniel, Ferrin, Michael A, Rangamani, Padmini, Drubin, David G
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041948/
https://www.ncbi.nlm.nih.gov/pubmed/31951196
http://dx.doi.org/10.7554/eLife.49840
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author Akamatsu, Matthew
Vasan, Ritvik
Serwas, Daniel
Ferrin, Michael A
Rangamani, Padmini
Drubin, David G
author_facet Akamatsu, Matthew
Vasan, Ritvik
Serwas, Daniel
Ferrin, Michael A
Rangamani, Padmini
Drubin, David G
author_sort Akamatsu, Matthew
collection PubMed
description 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.
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spelling pubmed-70419482020-02-27 Principles of self-organization and load adaptation by the actin cytoskeleton during clathrin-mediated endocytosis Akamatsu, Matthew Vasan, Ritvik Serwas, Daniel Ferrin, Michael A Rangamani, Padmini Drubin, David G eLife Cell Biology 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. eLife Sciences Publications, Ltd 2020-01-17 /pmc/articles/PMC7041948/ /pubmed/31951196 http://dx.doi.org/10.7554/eLife.49840 Text en © 2020, Akamatsu et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Akamatsu, Matthew
Vasan, Ritvik
Serwas, Daniel
Ferrin, Michael A
Rangamani, Padmini
Drubin, David G
Principles of self-organization and load adaptation by the actin cytoskeleton during clathrin-mediated endocytosis
title Principles of self-organization and load adaptation by the actin cytoskeleton during clathrin-mediated endocytosis
title_full Principles of self-organization and load adaptation by the actin cytoskeleton during clathrin-mediated endocytosis
title_fullStr Principles of self-organization and load adaptation by the actin cytoskeleton during clathrin-mediated endocytosis
title_full_unstemmed Principles of self-organization and load adaptation by the actin cytoskeleton during clathrin-mediated endocytosis
title_short Principles of self-organization and load adaptation by the actin cytoskeleton during clathrin-mediated endocytosis
title_sort principles of self-organization and load adaptation by the actin cytoskeleton during clathrin-mediated endocytosis
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041948/
https://www.ncbi.nlm.nih.gov/pubmed/31951196
http://dx.doi.org/10.7554/eLife.49840
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