A Mechanoresponsive Cadherin-Keratin Complex Directs Polarized Protrusive Behavior and Collective Cell Migration

• Published in: Developmental cell Vol. 22; no. 1; pp. 104 - 115
• Main Authors: Weber, Gregory F., Bjerke, Maureen A., DeSimone, Douglas W.
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 17.01.2012; Cell Press
• Subjects: Actins - metabolism; alpha Catenin - metabolism; Animals; Biological and medical sciences; Blotting, Western; Cadherins - genetics; Cadherins - metabolism; Cell Adhesion - physiology; Cell Communication; Cell differentiation, maturation, development, hematopoiesis; Cell Membrane - metabolism; Cell Movement - physiology; Cell physiology; Cell Polarity; Cell Surface Extensions - physiology; Cells, Cultured; Cytoskeleton - metabolism; Embryo, Nonmammalian - cytology; Embryo, Nonmammalian - metabolism; Female; Fluorescent Antibody Technique; Fundamental and applied biological sciences. Psychology; gamma Catenin - metabolism; Keratins - metabolism; Mechanotransduction, Cellular - physiology; Molecular and cellular biology; Real-Time Polymerase Chain Reaction; RNA, Messenger - genetics; Stress, Mechanical; Xenopus laevis - embryology; Xenopus laevis - metabolism; Xenopus Proteins - genetics; Xenopus Proteins - metabolism; Development; Keratin; Behavior; Cadherin; Cell migration; Cell adhesion molecule
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2011.10.013

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. [Display omitted] [Display omitted] ► Tensile force on cadherins induces polarity of migration in the opposite direction ► Keratin filaments and plakoglobin are recruited to mechanically stimulated cadherins ► Keratin and plakoglobin are required for mechanoresponsive cell behavior