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Deciphering the molecular mechanisms of actin cytoskeleton regulation in cell migration using cryo-EM
The actin cytoskeleton plays a key role in cell migration and cellular morphodynamics in most eukaryotes. The ability of the actin cytoskeleton to assemble and disassemble in a spatiotemporally controlled manner allows it to form higher-order structures, which can generate forces required for a cell...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9987995/ https://www.ncbi.nlm.nih.gov/pubmed/36695514 http://dx.doi.org/10.1042/BST20220221 |
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author | Fäßler, Florian Javoor, Manjunath G. Schur, Florian KM |
author_facet | Fäßler, Florian Javoor, Manjunath G. Schur, Florian KM |
author_sort | Fäßler, Florian |
collection | PubMed |
description | The actin cytoskeleton plays a key role in cell migration and cellular morphodynamics in most eukaryotes. The ability of the actin cytoskeleton to assemble and disassemble in a spatiotemporally controlled manner allows it to form higher-order structures, which can generate forces required for a cell to explore and navigate through its environment. It is regulated not only via a complex synergistic and competitive interplay between actin-binding proteins (ABP), but also by filament biochemistry and filament geometry. The lack of structural insights into how geometry and ABPs regulate the actin cytoskeleton limits our understanding of the molecular mechanisms that define actin cytoskeleton remodeling and, in turn, impact emerging cell migration characteristics. With the advent of cryo-electron microscopy (cryo-EM) and advanced computational methods, it is now possible to define these molecular mechanisms involving actin and its interactors at both atomic and ultra-structural levels in vitro and in cellulo. In this review, we will provide an overview of the available cryo-EM methods, applicable to further our understanding of the actin cytoskeleton, specifically in the context of cell migration. We will discuss how these methods have been employed to elucidate ABP- and geometry-defined regulatory mechanisms in initiating, maintaining, and disassembling cellular actin networks in migratory protrusions. |
format | Online Article Text |
id | pubmed-9987995 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-99879952023-03-07 Deciphering the molecular mechanisms of actin cytoskeleton regulation in cell migration using cryo-EM Fäßler, Florian Javoor, Manjunath G. Schur, Florian KM Biochem Soc Trans Review Articles The actin cytoskeleton plays a key role in cell migration and cellular morphodynamics in most eukaryotes. The ability of the actin cytoskeleton to assemble and disassemble in a spatiotemporally controlled manner allows it to form higher-order structures, which can generate forces required for a cell to explore and navigate through its environment. It is regulated not only via a complex synergistic and competitive interplay between actin-binding proteins (ABP), but also by filament biochemistry and filament geometry. The lack of structural insights into how geometry and ABPs regulate the actin cytoskeleton limits our understanding of the molecular mechanisms that define actin cytoskeleton remodeling and, in turn, impact emerging cell migration characteristics. With the advent of cryo-electron microscopy (cryo-EM) and advanced computational methods, it is now possible to define these molecular mechanisms involving actin and its interactors at both atomic and ultra-structural levels in vitro and in cellulo. In this review, we will provide an overview of the available cryo-EM methods, applicable to further our understanding of the actin cytoskeleton, specifically in the context of cell migration. We will discuss how these methods have been employed to elucidate ABP- and geometry-defined regulatory mechanisms in initiating, maintaining, and disassembling cellular actin networks in migratory protrusions. Portland Press Ltd. 2023-02-27 2023-01-25 /pmc/articles/PMC9987995/ /pubmed/36695514 http://dx.doi.org/10.1042/BST20220221 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Review Articles Fäßler, Florian Javoor, Manjunath G. Schur, Florian KM Deciphering the molecular mechanisms of actin cytoskeleton regulation in cell migration using cryo-EM |
title | Deciphering the molecular mechanisms of actin cytoskeleton regulation in cell migration using cryo-EM |
title_full | Deciphering the molecular mechanisms of actin cytoskeleton regulation in cell migration using cryo-EM |
title_fullStr | Deciphering the molecular mechanisms of actin cytoskeleton regulation in cell migration using cryo-EM |
title_full_unstemmed | Deciphering the molecular mechanisms of actin cytoskeleton regulation in cell migration using cryo-EM |
title_short | Deciphering the molecular mechanisms of actin cytoskeleton regulation in cell migration using cryo-EM |
title_sort | deciphering the molecular mechanisms of actin cytoskeleton regulation in cell migration using cryo-em |
topic | Review Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9987995/ https://www.ncbi.nlm.nih.gov/pubmed/36695514 http://dx.doi.org/10.1042/BST20220221 |
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