title: mDia2 regulates actin and focal adhesion dynamics and organization in the lamella for efficient epithelial cell migration.
abstract: Cell migration requires spatial and temporal regulation of filamentous actin (F-actin) dynamics. This regulation is achieved by distinct actin-associated proteins, which mediate polymerization, depolymerization, severing, contraction, bundling or engagement to the membrane. Mammalian Diaphanous-related (mDia) formins, which nucleate, processively elongate, and in some cases bundle actin filaments, have been extensively studied in vitro, but their function in the cell has been less well characterized. Here we study the role of mDia2 activity in the dynamic organization of F-actin in migrating epithelial cells. We find that mDia2 localizes in the lamella of migrating epithelial cells, where it is involved in the formation of a stable pool of cortical actin and in maintenance of polymerization-competent free filament barbed ends at focal adhesions. Specific inhibition of mDia2 alters focal adhesion turnover and reduces migration velocity. We suggest that the regulation of filament assembly dynamics at focal adhesions may be necessary for the formation of a stable pool of cortical lamella actin and the proper assembly and disassembly dynamics of focal adhesions, making mDia2 an important factor in epithelial cell migration.
authors.affiliation: Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Gupton
authors.forename: Kathryn
authors.initials: K
authors.lastname: Eisenmann
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Alberts
authors.forename: Clare M
authors.initials: CM
authors.lastname: Waterman-Storer
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D048430:Cell Shape; D022081:Cell Surface Extensions / Q000378:metabolism* / Q000648:ultrastructure; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D022001:Focal Adhesions / Q000378:metabolism*; D000080865:Formins; D006801:Humans
chemical_list: D000199:Actins; D002352:Carrier Proteins; C491462:DIAPH2 protein, human; D000080865:Formins