Forced to Signal

Science Signaling  08 Jun 2010:
Vol. 3, Issue 125, pp. ec167
DOI: 10.1126/scisignal.3125ec167

Cells sense their contact with a substrate or with other cells through specialized adhesion molecules on the cell surface. Tightly associated epithelial cells connect to adjacent cells through cadherin proteins, which interact with many other proteins at adherens junctions. Yonemura et al. show that one of these associated proteins, α-catenin, appears to serve as a mechanosensor, converting tension generated through myosin II and filamentous actin into a biochemical signal at points of cell adhesion. The protein vinculin associates with adherens junctions in a way that requires tension within the actin cytoskeleton. The authors confirmed in various mouse and human epithelial cell lines that association of vinculin with adherens junctions was lost if activity of myosin II was blocked. Studies with cells expressing various fragments of α-catenin indicated that a region of α-catenin normally blocked vinculin binding but that inhibition was relieved when α-catenin could bind to actin filaments through its C terminus. Thus, the authors propose that tension stretches the α-catenin molecule in a way that exposes a vinculin binding site. They also identified an antibody that appears to specifically recognize this “open” conformation of α-catenin. In a wound-healing model in which cells form contractile rings to close the wound, the antibody specifically bound to adherens junctions where tension was high and vinculin was recruited. The authors propose that this mechanism can explain the particular localization of adherens junctions in specific areas of the lateral membranes of epithelial cell sheets and may work to balance forces that adjacent cells placed on one another. Lecuit provides commentary.

S. Yonemura, Y. Wada, T. Watanabe, A. Nagafuchi, M. Shibata, α-Catenin as a tension transducer that induces adherens junction development. Nat. Cell Biol. 12, 533–542 (2010). [PubMed]

T. Lecuit, α-Catenin mechanosensing for adherens junctions. Nat. Cell Biol. 12, 522–524 (2010). [PubMed]