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Publication : Mechanical instability of adherens junctions overrides intrinsic quiescence of hair follicle stem cells.

First Author  Biswas R Year  2021
Journal  Dev Cell Volume  56
Issue  6 Pages  761-780.e7
PubMed ID  33725480 Mgi Jnum  J:303710
Mgi Id  MGI:6515852 Doi  10.1016/j.devcel.2021.02.020
Citation  Biswas R, et al. (2021) Mechanical instability of adherens junctions overrides intrinsic quiescence of hair follicle stem cells. Dev Cell 56(6):761-780.e7
abstractText  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 alpha-catenin. Mechanistically, we demonstrate that vinculin functions by keeping alpha-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.
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