학술논문
Cdc42 activity in the trailing edge is required for persistent directional migration of keratinocytes.
Document Type
Academic Journal
Author
Patwardhan R; Department of Molecular Cell Biology, Center of Medical Biotechnology, University of Duisburg-Essen, 45141 Essen, Germany.; Nanda S; TU Dortmund University, Fakultät für Chemie und Chemische Biologie, 44227 Dortmund, Germany.; Wagner J; Department of Molecular Cell Biology, Center of Medical Biotechnology, University of Duisburg-Essen, 45141 Essen, Germany.; Stockter T; Department of Molecular Cell Biology, Center of Medical Biotechnology, University of Duisburg-Essen, 45141 Essen, Germany.; Dehmelt L; TU Dortmund University, Fakultät für Chemie und Chemische Biologie, 44227 Dortmund, Germany.; Nalbant P; Department of Molecular Cell Biology, Center of Medical Biotechnology, University of Duisburg-Essen, 45141 Essen, Germany.
Source
Publisher: American Society for Cell Biology Country of Publication: United States NLM ID: 9201390 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1939-4586 (Electronic) Linking ISSN: 10591524 NLM ISO Abbreviation: Mol Biol Cell Subsets: MEDLINE
Subject
Language
English
Abstract
Fibroblasts migrate discontinuously by generating transient leading-edge protrusions and irregular, abrupt retractions of a narrow trailing edge. In contrast, keratinocytes migrate persistently and directionally via a single, stable, broad protrusion paired with a stable trailing-edge. The Rho GTPases Rac1, Cdc42 and RhoA are key regulators of cell protrusions and retractions. However, how these molecules mediate cell-type specific migration modes is still poorly understood. In fibroblasts, all three Rho proteins are active at the leading edge, suggesting short-range coordination of protrusive Rac1 and Cdc42 signals with RhoA retraction signals. Here, we show that Cdc42 was surprisingly active in the trailing-edge of migrating keratinocytes. Elevated Cdc42 activity colocalized with the effectors MRCK and N-WASP suggesting that Cdc42 controls both myosin activation and actin polymerization in the back. Indeed, Cdc42 was required to maintain the highly dynamic contractile acto-myosin retrograde flow at the trailing edge of keratinocytes, and its depletion induced ectopic protrusions in the back, leading to decreased migration directionality. These findings suggest that Cdc42 is required to stabilize the dynamic cytoskeletal polarization in keratinocytes, to enable persistent, directional migration.