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

  1. Pavan Vedula
  2. Satoshi Kurosaka
  3. Brittany MacTaggart
  4. Qin Ni
  5. Garegin Papoian
  6. Yi Jiang
  7. Dawei Dong
  8. Anna Kashina  Is a corresponding author
  1. University of Pennsylvania, United States
  2. University of Maryland, United States
  3. 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

The following data sets were generated

Article and author information

Author details

  1. Pavan Vedula

    Department of Biomedical Sciences, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9914-0008
  2. Satoshi Kurosaka

    Department of Biomedical Sciences, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4365-9003
  3. Brittany MacTaggart

    Department of Biomedical Sciences, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7674-6042
  4. Qin Ni

    Chemical and Molecular Engineering, University of Maryland, College Park, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Garegin Papoian

    Chemistry, University of Maryland, College Park, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Yi Jiang

    Mathematics and Statistics, Georgia State University, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Dawei Dong

    Department of Biomedical Sciences, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Anna Kashina

    Department of Biomedical Sciences, University of Pennsylvania, Philadelphia, United States
    For correspondence
    akashina@upenn.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0243-6866

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

  1. Robert H Singer, Albert Einstein College of Medicine, United States

Publication history

  1. Received: March 23, 2021
  2. Accepted: June 19, 2021
  3. Accepted Manuscript published: June 24, 2021 (version 1)
  4. Version of Record published: August 2, 2021 (version 2)
  5. 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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  1. Pavan Vedula
  2. Satoshi Kurosaka
  3. Brittany MacTaggart
  4. Qin Ni
  5. Garegin Papoian
  6. Yi Jiang
  7. Dawei Dong
  8. Anna Kashina
(2021)
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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