RT Journal Article
SR Electronic
T1 Persistent cell motility requires transcriptional feedback of cytoskeletal – focal adhesion equilibrium by YAP/TAZ
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 265744
DO 10.1101/265744
A1 Devon E. Mason
A1 James H. Dawahare
A1 Trung Dung Nguyen
A1 Yang Lin
A1 Sherry L. Voytik-Harbin
A1 Pinar Zorlutuna
A1 Mervin E. Yoder
A1 Joel D. Boerckel
YR 2018
UL http://biorxiv.org/content/early/2018/02/14/265744.abstract
AB 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 co-activators 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 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 enable neovascular function.