Formin-mediated Actin Polymerization and Cadherin-mediated cell-cell adhesion [Completed Project]

E-Cadherin-mediated Adherens Junctions (AJs) in epithelial cells are anchoring junctions that help connect cells in a tissue by bridging the cytoskeleton of neighboring cells. Binding to the cytoskeleton allows these junctions to function as force-sensors and participate in morphogenesis, migration, tissue repair and regeneration. The formin family of actin nucleators (that is, proteins that build the actin cytoskeleton) is implicated in generating several cellular actin structures; however, their role at AJs remains poorly characterized. Using mammalian epithelial cells in culture, we elucidated the role of actin polymerization mediated by formins in regulating E-Cadherin clustering and dynamics at AJs. We identifed mDia1 and Fmnl3 as major factors enhancing actin polymerization and stabilizing E-cadherin at epithelial junctions. Fmnl3 localizes to adherens junctions downstream of Src and Cdc42 and its depletion leads to a reduction in F-actin and E-cadherin at junctions and a weakening of cell–cell adhesion. Of importance, Fmnl3 expression is up-regulated and junctional localization increases during collective cell migration. Depletion of Fmnl3 or mDia1 in migrating monolayers results in dissociation of leader cells and impaired wound repair. These results were published in Molecular Biology of the Cell 27(18):2844-56. doi: 10.1091/mbc.E16-06-0429.

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