Mechanical instability of adherens junctions overrides intrinsic quiescence of hair follicle stem cells.
|Mechanical instability of adherens junctions overrides intrinsic quiescence of hair follicle stem cells.
|Year of Publication
|Biswas R, Banerjee A, Lembo S, Zhao Z, Lakshmanan V, Lim R, Le S, Nakasaki M, Kutyavin V, Wright G, Palakodeti D, Ross RS, Jamora C, Vasioukhin V, Jie Y, Raghavan S
|2021 Mar 22
Vinculin, a mechanotransducer associated with both adherens junctions (AJs) and focal adhesions (FAs), plays a central role in force transmission through cell-cell and cell-substratum contacts. We generated the conditional knockout (cKO) of vinculin in murine skin that results in the loss of bulge stem cell (BuSC) quiescence and promotes continual cycling of the hair follicles. Surprisingly, we find that the AJs in vinculin cKO cells are mechanically weak and impaired in force generation despite increased junctional expression of E-cadherin and α-catenin. Mechanistically, we demonstrate that vinculin functions by keeping α-catenin in a stretched/open conformation, which in turn regulates the retention of YAP1, another potent mechanotransducer and regulator of cell proliferation, at the AJs. Altogether, our data provide mechanistic insights into the hitherto-unexplored regulatory link between the mechanical stability of cell junctions and contact-inhibition-mediated maintenance of BuSC quiescence.
|R01 CA179914 / CA / NCI NIH HHS / United States
R01 CA188452 / CA / NCI NIH HHS / United States
R01 CA234050 / CA / NCI NIH HHS / United States