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

eLife

Brittany MacTaggart¹  Anna Kashina¹  Pavan Vedula¹  Dawei Dong²  Qin Ni³  Garegin Papoian⁴  Yi Jiang⁵  Satoshi Kurosaka⁶ 

[1] Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, United States;Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, United States;Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States;Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, United States;Department of Chemistry, University of Maryland, College Park, United States;Department of Mathematics and Statistics, Georgia State University, Atlanta, United States;Institute of Advanced Technology, Kindai University, Kainan, Wakayama, Japan;

关键词: actin isoforms;    translation rate;    coding sequence;    cell migration;    Mouse;   

DOI  :  10.7554/eLife.68712

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY