title: Formin-mediated actin polymerization at cell-cell junctions stabilizes E-cadherin and maintains monolayer integrity during wound repair.
abstract: Cadherin-mediated cell-cell adhesion is required for epithelial tissue integrity in homeostasis, during development, and in tissue repair. E-cadherin stability depends on F-actin, but the mechanisms regulating actin polymerization at cell-cell junctions remain poorly understood. Here we investigated a role for formin-mediated actin polymerization at cell-cell junctions. We identify 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. In summary, our results show that formin activity at epithelial cell-cell junctions is important for adhesion and the maintenance of epithelial cohesion during dynamic processes, such as wound repair.
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411.
authors.forename: Megha Vaman
authors.initials: MV
authors.lastname: Rao
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411 Department of Biomedical Engineering, National University of Singapore, Singapore 117575 biezbr@nus.edu.sg.
authors.forename: Ronen
authors.initials: R
authors.lastname: Zaidel-Bar
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism* / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D004847:Epithelial Cells / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005326:Fetal Proteins / Q000378:metabolism; D000080865:Formins; D007365:Intercellular Junctions / Q000378:metabolism; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D058105:Polymerization; D011506:Proteins / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology; D014947:Wounds and Injuries / Q000378:metabolism
chemical_list: D000199:Actins; D015820:Cadherins; D002352:Carrier Proteins; C491464:Diap1 protein, mouse; C570808:FMNL3 protein, mouse; D005326:Fetal Proteins; D000080865:Formins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D011506:Proteins