Mechanical Instability of Adherens Junctions Overrides Intrinsic Quiescence of Hair Follicle Stem Cells

Vinculin, a mechanotransducer associated with both adherens junctions (AJ) and focal adhesions (FA) plays a central role in force transmission through these cell-cell and cell-substratum contacts. The conditional knock out (KO) of vinculin in murine skin results in the loss of bulge stem cell (BuSC) quiescence and hair follicles that cycle continually. Remarkably, we find that the AJs in vinculin KO cells are mechanically weak and impaired in force generation despite increased expression of E-cadherin and α-catenin at the junctions. Mechanistically, 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, to the junctions.  Altogether, our data provides definitive mechanistic insights into the hitherto unexplored regulatory link between the mechanical stability of cell-junctions and the maintenance of BuSC quiescence via contact inhibition.