title: A role for gelsolin in stress fiber-dependent cell contraction.
abstract: Gelsolin is an abundant actin binding protein that mediates the rapid remodeling of cortical actin filaments through severing, capping, and nucleating activities. Most of the attention on the intracellular function of gelsolin has focused on the remodeling of the cortical actin meshwork but the localization of gelsolin to other regions of the cell suggests that it may have other important functions elsewhere. In cultured fibroblasts, gelsolin is heavily enriched in stress fibers, where its function in these contractile organelles is unknown. To study gelsolin function during stress fiber formation and cell contraction, we first assessed gelsolin levels in stress fiber preparations from lysophosphatidic acid (LPA)-treated human fibroblasts. LPA induced a large, time-dependent, calcium-independent increase of actin, gelsolin, alpha-actinin, and tropomyosin in stress fiber preparations. A microinjected gelsolin antibody that inhibits severing by gelsolin reduced stress fibers. Anti-sense-transfected gelsolin-depleted 3T3 cell lines treated with LPA after serum starvation required approximately 6 h to form stress fibers and focal adhesions, in contrast to control lines transfected with vector only, which formed stress fibers 15 min after addition of LPA. In cells microinjected with the gelsolin antibody that inhibits severing, Mg-ATP-induced cell contraction was greatly reduced in approximately 90% of injected cells compared to cells injected with an irrelevant antibody. Gelsolin-depleted cells were incapable of collagen gel contraction and showed no apparent Mg-ATP-induced cell contraction compared to cell lines transfected with vector only. The involvement of gelsolin in cell contraction and remodeling of collagen gels suggests a novel role for gelsolin in stress fiber-dependent cell function.
authors.affiliation: Faculty of Dentistry, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
authors.forename: P D
authors.initials: PD
authors.lastname: Arora
authors.forename: P A
authors.initials: PA
authors.lastname: Janmey
authors.forename: C A
authors.initials: CA
authors.lastname: McCulloch
mesh_terms: D016475:3T3 Cells; D008841:Actin Cytoskeleton / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D018260:Gelsolin / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology; D051379:Mice
chemical_list: D018260:Gelsolin; D008246:Lysophospholipids