YAP and TAZ limit cytoskeletal and focal adhesion maturation to enable persistent cell motility
Year: 2019
Type: article
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.
Source: The Journal of Cell Biology
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: hybrid
Awards: G1199548893, Indiana Clinical and Translational Sciences Institute, G4481177325, Comparing the Roles of Bone Cells and Marrow Cells in the Adaptive Response of Bone to Loading, G6717099065, Mechanical Control of Therapeutic Vasculogenesis for Peripheral Ischemia, CAREER:Tissue-engineering an aging heart: The effect of aged cell microenvironment in myocardial infarction, G932438427, Science and Technology Center for Engineering Mechano-Biology
OpenAlex ID: W2913470460