Mechanistic insights into actin force generation during vesicle formation from cryo-electron tomography
| Autor: | Daniel Serwas, Matthew Akamatsu, Amir Moayed, Karthik Vegesna, Ritvik Vasan, Jennifer M. Hill, Johannes Schöneberg, Karen M. Davies, Padmini Rangamani, David G. Drubin |
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| Rok vydání: | 2021 |
| Předmět: |
Electron Microscope Tomography
1.1 Normal biological development and functioning clathrin-mediated endocytosis Medical and Health Sciences General Biochemistry Genetics and Molecular Biology Article lipids trafficking Underpinning research Humans theory Molecular Biology Cytoskeleton mathematical modeling cytoskeleton Cell Biology Biological Sciences cryo-electron tomography Actins Clathrin Endocytosis Actin Cytoskeleton Generic health relevance actin Developmental Biology |
| Zdroj: | Dev Cell Developmental cell, vol 57, iss 9 |
| ISSN: | 1878-1551 |
| Popis: | 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 ameasured branch angle indicate that sufficient force to drive membrane internalization is generated throughpolymerization 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. |
| Databáze: | OpenAIRE |
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