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Different translation dynamics of β- and γ-actin regulates cell migration

β- and γ-cytoplasmic actins are ubiquitously expressed in every cell type and are nearly identical at the amino acid level but play vastly different roles in vivo. Their essential roles in embryogenesis and mesenchymal cell migration critically depend on the nucleotide sequences of their genes, rath...

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Autores principales: Vedula, Pavan, Kurosaka, Satoshi, MacTaggart, Brittany, Ni, Qin, Papoian, Garegin, Jiang, Yi, Dong, Dawei W, Kashina, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328520/
https://www.ncbi.nlm.nih.gov/pubmed/34165080
http://dx.doi.org/10.7554/eLife.68712
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author Vedula, Pavan
Kurosaka, Satoshi
MacTaggart, Brittany
Ni, Qin
Papoian, Garegin
Jiang, Yi
Dong, Dawei W
Kashina, Anna
author_facet Vedula, Pavan
Kurosaka, Satoshi
MacTaggart, Brittany
Ni, Qin
Papoian, Garegin
Jiang, Yi
Dong, Dawei W
Kashina, Anna
author_sort Vedula, Pavan
collection PubMed
description β- and γ-cytoplasmic actins are ubiquitously expressed in every cell type and are nearly identical at the amino acid level but play vastly different roles in vivo. Their essential roles in embryogenesis and mesenchymal cell migration critically depend on the nucleotide sequences of their genes, rather than their amino acid sequences; however, it is unclear which gene elements underlie this effect. Here we address the specific role of the coding sequence in β- and γ-cytoplasmic actins’ intracellular functions, using stable polyclonal populations of immortalized mouse embryonic fibroblasts with exogenously expressed actin isoforms and their ‘codon-switched’ variants. When targeted to the cell periphery using β-actin 3′UTR; β-actin and γ-actin have differential effects on cell migration. These effects directly depend on the coding sequence. Single-molecule measurements of actin isoform translation, combined with fluorescence recovery after photobleaching, demonstrate a pronounced difference in β- and γ-actins’ translation elongation rates in cells, leading to changes in their dynamics at focal adhesions, impairments in actin bundle formation, and reduced cell anchoring to the substrate during migration. Our results demonstrate that coding sequence-mediated differences in actin translation play a key role in cell migration.
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spelling pubmed-83285202021-08-04 Different translation dynamics of β- and γ-actin regulates cell migration Vedula, Pavan Kurosaka, Satoshi MacTaggart, Brittany Ni, Qin Papoian, Garegin Jiang, Yi Dong, Dawei W Kashina, Anna eLife Cell Biology β- and γ-cytoplasmic actins are ubiquitously expressed in every cell type and are nearly identical at the amino acid level but play vastly different roles in vivo. Their essential roles in embryogenesis and mesenchymal cell migration critically depend on the nucleotide sequences of their genes, rather than their amino acid sequences; however, it is unclear which gene elements underlie this effect. Here we address the specific role of the coding sequence in β- and γ-cytoplasmic actins’ intracellular functions, using stable polyclonal populations of immortalized mouse embryonic fibroblasts with exogenously expressed actin isoforms and their ‘codon-switched’ variants. When targeted to the cell periphery using β-actin 3′UTR; β-actin and γ-actin have differential effects on cell migration. These effects directly depend on the coding sequence. Single-molecule measurements of actin isoform translation, combined with fluorescence recovery after photobleaching, demonstrate a pronounced difference in β- and γ-actins’ translation elongation rates in cells, leading to changes in their dynamics at focal adhesions, impairments in actin bundle formation, and reduced cell anchoring to the substrate during migration. Our results demonstrate that coding sequence-mediated differences in actin translation play a key role in cell migration. eLife Sciences Publications, Ltd 2021-06-24 /pmc/articles/PMC8328520/ /pubmed/34165080 http://dx.doi.org/10.7554/eLife.68712 Text en © 2021, Vedula 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
Vedula, Pavan
Kurosaka, Satoshi
MacTaggart, Brittany
Ni, Qin
Papoian, Garegin
Jiang, Yi
Dong, Dawei W
Kashina, Anna
Different translation dynamics of β- and γ-actin regulates cell migration
title Different translation dynamics of β- and γ-actin regulates cell migration
title_full Different translation dynamics of β- and γ-actin regulates cell migration
title_fullStr Different translation dynamics of β- and γ-actin regulates cell migration
title_full_unstemmed Different translation dynamics of β- and γ-actin regulates cell migration
title_short Different translation dynamics of β- and γ-actin regulates cell migration
title_sort different translation dynamics of β- and γ-actin regulates cell migration
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328520/
https://www.ncbi.nlm.nih.gov/pubmed/34165080
http://dx.doi.org/10.7554/eLife.68712
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