Multiparametric Analysis of Cell Shape Demonstrates that β-PIX Directly Couples YAP Activation to Extracellular Matrix Adhesion
Mechanical signals from the extracellular matrix (ECM) and cellular geometry regulate the nuclear translocation of transcriptional regulators such as Yes-associated protein (YAP). Elucidating how physical signals control the activity of mechanosensitive proteins poses a technical challenge, because perturbations that affect cell shape may also affect protein localization indirectly. Here, we present an approach that mitigates confounding effects of cell-shape changes, allowing us to identify direct regulators of YAP localization. This method uses single-cell image analysis and statistical models that exploit the naturally occurring heterogeneity of cellular populations. Through systematic depletion of all human kinases, Rho family GTPases, GEFs, and GTPase activating proteins (GAPs), together with targeted chemical perturbations, we found that β-PIX, a Rac1/Ccd42 GEF, and PAK2, a Rac1/Cdc42 effector, drive both YAP activation and cell-ECM adhesion turnover during cell spreading. Our observations suggest that coupling YAP to adhesion dynamics acts as a mechano-timer, allowing cells to rapidly tune gene expression in response to physical signals.
원문복사신청을 하시면, 일부 해외 인쇄학술지의 경우 외국학술지지원센터(FRIC)에서
무료 원문복사 서비스를 제공합니다.
NDSL에서는 해당 원문을 복사서비스하고 있습니다. 위의 원문복사신청 또는 장바구니 담기를 통하여 원문복사서비스 이용이 가능합니다.
- 이 논문과 함께 출판된 논문 + 더보기