title: A mechanoresponsive cadherin-keratin complex directs polarized protrusive behavior and collective cell migration.
abstract: Collective cell migration requires maintenance of adhesive contacts between adjacent cells, coordination of polarized cell protrusions, and generation of propulsive traction forces. We demonstrate that mechanical force applied locally to C-cadherins on single Xenopus mesendoderm cells is sufficient to induce polarized cell protrusion and persistent migration typical of individual cells within a collectively migrating tissue. Local tension on cadherin adhesions induces reorganization of the keratin intermediate filament network toward these stressed sites. Plakoglobin, a member of the catenin family, is localized to cadherin adhesions under tension and is required for both mechanoresponsive cell behavior and assembly of the keratin cytoskeleton at the rear of these cells. Local tugging forces on cadherins occur in vivo through interactions with neighboring cells, and these forces result in coordinate changes in cell protrusive behavior. Thus, cadherin-dependent force-inducible regulation of cell polarity in single mesendoderm cells represents an emergent property of the intact tissue.
authors.affiliation: Department of Cell Biology, School of Medicine, University of Virginia Health System, Charlottesville, VA 22908, USA.
authors.forename: Gregory F
authors.initials: GF
authors.lastname: Weber
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Bjerke
authors.forename: Douglas W
authors.initials: DW
authors.lastname: DeSimone
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D016764:Cell Polarity; D022081:Cell Surface Extensions / Q000502:physiology*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D007633:Keratins / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D013314:Stress, Mechanical; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology / Q000378:metabolism*; D051178:alpha Catenin / Q000378:metabolism; D051185:gamma Catenin / Q000378:metabolism
chemical_list: D000199:Actins; C074260:CDH3 protein, Xenopus; D015820:Cadherins; D012333:RNA, Messenger; D029867:Xenopus Proteins; D051178:alpha Catenin; D051185:gamma Catenin; D007633:Keratins