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 Yoder, Joel D. Boerckel

Research output: Contribution to journalArticle

4 Citations (Scopus)

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
JournalThe Journal of cell biology
Volume218
Issue number4
DOIs
StatePublished - Apr 1 2019

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Focal Adhesions
Cell Movement
Myosin-Light-Chain Phosphatase
Myosin Type II
Actomyosin
Traction
Mechanics
Gene Expression

ASJC Scopus subject areas

  • Cell Biology

Cite this

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

YAP and TAZ limit cytoskeletal and focal adhesion maturation to enable persistent cell motility. / Mason, Devon E.; Collins, Joseph M.; Dawahare, James H.; Nguyen, Trung Dung; Lin, Yang; Voytik-Harbin, Sherry L.; Zorlutuna, Pinar; Yoder, Mervin; Boerckel, Joel D.

In: The Journal of cell biology, Vol. 218, No. 4, 01.04.2019, p. 1369-1389.

Research output: Contribution to journalArticle

Mason, DE, Collins, JM, Dawahare, JH, Nguyen, TD, Lin, Y, Voytik-Harbin, SL, Zorlutuna, P, Yoder, M & Boerckel, JD 2019, 'YAP and TAZ limit cytoskeletal and focal adhesion maturation to enable persistent cell motility', The Journal of cell biology, vol. 218, no. 4, pp. 1369-1389. https://doi.org/10.1083/jcb.201806065
Mason DE, Collins JM, Dawahare JH, Nguyen TD, Lin Y, Voytik-Harbin SL et al. YAP and TAZ limit cytoskeletal and focal adhesion maturation to enable persistent cell motility. The Journal of cell biology. 2019 Apr 1;218(4):1369-1389. https://doi.org/10.1083/jcb.201806065
Mason, Devon E. ; Collins, Joseph M. ; Dawahare, James H. ; Nguyen, Trung Dung ; Lin, Yang ; Voytik-Harbin, Sherry L. ; Zorlutuna, Pinar ; Yoder, Mervin ; Boerckel, Joel D. / YAP and TAZ limit cytoskeletal and focal adhesion maturation to enable persistent cell motility. In: The Journal of cell biology. 2019 ; Vol. 218, No. 4. pp. 1369-1389.
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