YAP and TAZ limit cytoskeletal and focal adhesion maturation to enable persistent cell motility

Devon E. Mason, Joseph M. Collins, James H. Dawahare, Trung Dung Nguyen, Yang Lin, Sherry L. Voytik-Harbin, Pinar Zorlutuna, Mervin C. Yoder, Joel D. Boerckel

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Cell migration initiates by traction generation through reciprocal actomyosin tension and focal adhesion reinforcement, but continued motility requires adaptive cytoskeletal remodeling and adhesion release. Here, we asked whether de novo gene expression contributes to this cytoskeletal feedback. We found that global inhibition of transcription or translation does not impair initial cell polarization or migration initiation, but causes eventual migratory arrest through excessive cytoskeletal tension and over-maturation of focal adhesions, tethering cells to their matrix. The transcriptional coactivators YAP and TAZ mediate this feedback response, modulating cell mechanics by limiting cytoskeletal and focal adhesion maturation to enable persistent cell motility and 3D vasculogenesis. Motile arrest after YAP/TAZ ablation was partially rescued by depletion of the YAP/TAZ-dependent myosin phosphatase regulator, NUAK2, or by inhibition of Rho-ROCK-myosin II. Together, these data establish a transcriptional feedback axis necessary to maintain a responsive cytoskeletal equilibrium and persistent migration.

Original languageEnglish (US)
Pages (from-to)1369-1389
Number of pages21
JournalJournal of Cell Biology
Volume218
Issue number4
DOIs
StatePublished - Jan 1 2019

ASJC Scopus subject areas

  • Cell Biology

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    Mason, D. E., Collins, J. M., Dawahare, J. H., Nguyen, T. D., Lin, Y., Voytik-Harbin, S. L., Zorlutuna, P., Yoder, M. C., & Boerckel, J. D. (2019). YAP and TAZ limit cytoskeletal and focal adhesion maturation to enable persistent cell motility. Journal of Cell Biology, 218(4), 1369-1389. https://doi.org/10.1083/jcb.201806065