title: A hemidesmosomal protein regulates actin dynamics and traction forces in motile keratinocytes.
abstract: During wound healing of the skin, keratinocytes disassemble hemidesmosomes and reorganize their actin cytoskeletons in order to exert traction forces on and move directionally over the dermis. Nonetheless, the transmembrane hemidesmosome component collagen XVII (ColXVII) is found in actin-rich lamella, situated behind the lamellipodium. A set of actin bundles, along which ColXVII colocalizes with actinin4, is present at each lamella. Knockdown of either ColXVII or actinin4 not only inhibits directed migration of keratinocytes but also relieves constraints on actin bundle retrograde movement at the site of lamella, such that actin bundle movement is enhanced more than 5-fold. Moreover, whereas control keratinocytes move in a stepwise fashion over a substrate by generating alternating traction forces, of up to 1.4 kPa, at each flank of the lamellipodium, ColXVII knockdown keratinocytes fail to do so. In summary, our data indicate that ColXVII-actinin4 complexes at the lamella of a moving keratinocyte regulate actin dynamics, thereby determining the direction of cell movement.-Hiroyasu, S., Colburn, Z. T., Jones, J. C. R. A hemidesmosomal protein regulates actin dynamics and traction forces in motile keratinocytes.
authors.affiliation: School of Molecular Biosciences, Washington State University, Pullman, Washington, USA.
authors.forename: Sho
authors.initials: S
authors.lastname: Hiroyasu
authors.affiliation: School of Molecular Biosciences, Washington State University, Pullman, Washington, USA.
authors.forename: Zachary T
authors.initials: ZT
authors.lastname: Colburn
authors.affiliation: School of Molecular Biosciences, Washington State University, Pullman, Washington, USA jcr.jones@vetmed.wsu.edu.
authors.forename: Jonathan C R
authors.initials: JC
authors.lastname: Jones
mesh_terms: D000185:Actinin / Q000235:genetics / Q000378:metabolism; D000199:Actins / Q000502:physiology*; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D001696:Biomechanical Phenomena; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D000078404:Epidermal Cells; D005786:Gene Expression Regulation / Q000502:physiology*; D055785:Gene Knockdown Techniques; D022002:Hemidesmosomes / Q000502:physiology*; D006801:Humans; D015603:Keratinocytes / Q000502:physiology*; D024041:Non-Fibrillar Collagens / Q000235:genetics / Q000378:metabolism; D013499:Surface Properties; D000097805:Collagen Type XVII
chemical_list: D000185:Actinin; D000199:Actins; D001324:Autoantigens; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII; C111453:ACTN4 protein, human
keywords: cytoskeleton; lamella; lamellipodium; matrix adhesion; migration