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Junctional instability overrides intrinsic quiescence of bulge stem cells

Avinanda Banerjee

Vinculin, a mechano-transducer associated with both adherens junctions (AJ) and focal adhesions (FA), plays a central role in force transmission
through cell-cell and cell-substratum contacts. We generated the conditional knockout (KO) of vinculin in murine skin which 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 KO cells
are mechanically weak and impaired in force generation despite increased junctional expression of E-cadherin and a-catenin. Mechanistically,
we demonstrate that vinculin functions by keeping a-catenin in a stretched/open conformation, which in turn regulates the retention of YAP1,
another potent mechano-transducer and regulator of cell proliferation, at the AJs. Altogether, our data provides definitive mechanistic insights
into the hitherto unexplored regulatory link between the mechanical stability of cell junctions and contact inhibition-mediated maintenance of
BuSC quiescence.

Published Date: 2021-11-18;