2. Academic Validation
  3. YAP and TAZ limit cytoskeletal and focal adhesion maturation to enable persistent cell motility

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

  • J Cell Biol. 2019 Apr 1;218(4):1369-1389. doi: 10.1083/jcb.201806065.
Devon E Mason 1 2 3,  Joseph M Collins 1 2,  James H Dawahare 3,  Trung Dung Nguyen 3 4,  Yang Lin 5,  Sherry L Voytik-Harbin 6 7,  Pinar Zorlutuna 3,  Mervin C Yoder 5,  Joel D Boerckel 8 2 3
Affiliations

Affiliations

  • 1 McKay Orthopaedic Research Laboratory, Department of Orthopedic Surgery, University of Pennsylvania, Philadelphia, PA.
  • 2 Department of Bioengineering, University of Pennsylvania, Philadelphia, PA.
  • 3 Department of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, IN.
  • 4 Department of Engineering and Computer Science, Seattle Pacific University, Seattle, WA.
  • 5 Herman B. Wells Center for Pediatric Research, Indiana University, Indianapolis, IN.
  • 6 Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN.
  • 7 Department of Basic Medical Sciences, Purdue University, West Lafayette, IN.
  • 8 McKay Orthopaedic Research Laboratory, Department of Orthopedic Surgery, University of Pennsylvania, Philadelphia, PA boerckel@pennmedicine.upenn.edu.
PMID: 30737263 DOI: 10.1083/jcb.201806065
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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-15802
    98.03%, NUAK Kinase Inhibitor