Essential nucleotide- and protein-dependent functions of Actb/β-actin

Xiaobai Patrinostro, Pallabi Roy, Angus Lindsay, Christopher M Chamberlain, Lauren J. Sundby, Colby Starker, Daniel F Voytas, James M Ervasti, Benjamin J. Perrin

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

The highly similar cytoplasmic β- and γ-actins differ by only four functionally similar amino acids, yet previous in vitro and in vivo data suggest that they support unique functions due to striking phenotypic differences between Actb and Actg1 null mouse and cell models. To determine whether the four amino acid variances were responsible for the functional differences between cytoplasmic actins, we gene edited the endogenous mouse Actb locus to translate γ-actin protein. The resulting mice and primary embryonic fibroblasts completely lacked β-actin protein, but were viable and did not present with the most overt and severe cell and organismal phenotypes observed with gene knockout. Nonetheless, the edited mice exhibited progressive high-frequency hearing loss and degeneration of actin-based stereocilia as previously reported for hair cell-specific Actb knockout mice. Thus, β-actin protein is not required for general cellular functions, but is necessary to maintain auditory stereocilia.

Original languageEnglish (US)
Pages (from-to)7973-7978
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number31
DOIs
StatePublished - Jul 31 2018

Bibliographical note

Funding Information:
ACKNOWLEDGMENTS. We thank Dr. Kevin Sonnemann for his advice on the manuscript. This work was supported by NIH Grant AR049899 (to J.M.E.) and NIH Grant DC015495 (to B.J.P.).

Keywords

  • Auditory hair cell
  • Gene edited
  • Stereocilia
  • β-actin
  • γ-actin

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