Saturday, August 24, 2013

Mechanical Forces Regulate Signaling Proteins via Actin-Processing Factors to Control Cell Growth

Here is another good paper that shows how extracellular physical forces influence intracellular biochemistry and elicit cellular responses like proliferation. This is a growth area in cell biology.


A Mechanical Checkpoint Controls Multicellular Growth through YAP/TAZ Regulation by Actin-Processing Factors

Cell, 15 August 2013
Copyright © 2013 Elsevier Inc. All rights reserved.



  • Tissue form shapes epithelial growth pattern by YAP/TAZ regulation
  • A mechanical checkpoint controls contact inhibition of proliferation
  • F-actin-capping/severing proteins are epithelial gatekeepers limiting YAP/TAZ activity
  • Mechanical forces are overarching regulators of YAP/TAZ in multicellular contexts


Key cellular decisions, such as proliferation or growth arrest, typically occur at spatially defined locations within tissues. Loss of this spatial control is a hallmark of many diseases, including cancer. Yet, how these patterns are established is incompletely understood. Here, we report that physical and architectural features of a multicellular sheet inform cells about their proliferative capacity through mechanical regulation of YAP and TAZ, known mediators of Hippo signaling and organ growth. YAP/TAZ activity is confined to cells exposed to mechanical stresses, such as stretching, location at edges/curvatures contouring an epithelial sheet, or stiffness of the surrounding extracellular matrix. We identify the F-actin-capping/severing proteins Cofilin, CapZ, and Gelsolin as essential gatekeepers that limit YAP/TAZ activity in cells experiencing low mechanical stresses, including contact inhibition of proliferation. We propose that mechanical forces are overarching regulators of YAP/TAZ in multicellular contexts, setting responsiveness to Hippo, WNT, and GPCR signaling.

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