Different translation dynamics of β-and γ-actin regulates cell migration
- University of Pennsylvania, United States
- University of Maryland, United States
- Georgia State University, United States
Abstract
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 sequence, 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 the 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 the 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.
Data availability
Data generated or analyzed during this study are included in the manuscript and supporting files. Raw images and videos for the main text figures are available at the Dryad depository with the following unique identifier: doi:10.5061/dryad.z34tmpgd2
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Data from: Different translation dynamics of β-and γ-actin regulates cell migrationDryad Digital Repository, doi:10.5061/dryad.z34tmpgd2.
Article and author information
Author details
Brittany MacTaggart
Funding
National Institutes of Health (R35GM122505)
- Anna Kashina
National Institutes of Health (R01CA201340)
- Yi Jiang
National Institutes of Health (R01EY028450)
- Yi Jiang
National Science Foundation (CHE-1800418)
- Garegin Papoian
National Science Foundation (PHY-1806903)
- Garegin Papoian
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Robert H Singer, Albert Einstein College of Medicine, United States
Publication history
- Received: March 23, 2021
- Accepted: June 19, 2021
- Accepted Manuscript published: June 24, 2021 (version 1)
- Version of Record published: August 2, 2021 (version 2)
- Version of Record updated: August 3, 2021 (version 3)
Copyright
© 2021, Vedula et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Different translation dynamics of β-and γ-actin regulates cell migration
eLife 10:e68712.
https://doi.org/10.7554/eLife.68712
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