title: Gelsolin is a downstream effector of rac for fibroblast motility.
abstract: Rac, a member of the rho family of GTPases, when activated transmits signals leading to actin-based membrane ruffling in fibroblasts. Compared with wild-type fibroblasts, gelsolin null (Gsn-) dermal fibroblasts have a markedly reduced ruffling response to serum or EGF stimulation, which signal through rac. Bradykinin-induced filopodial formation, attributable to activation of cdc42, is similar in both cell types. Wild-type fibroblasts exhibit typical lamellipodial extension during translational locomotion, whereas Gsn- cells move 50% slower using structures resembling filopodia. Multiple Gsn- tissues as well as Gsn- fibroblasts overexpress rac, but not cdc42 or rho, 5-fold. Re-expression of gelsolin in Gsn- fibroblasts by stable transfection or adenovirus reverts the ruffling response, translational motility and rac expression to normal. Rac migrates to the cell membrane following EGF stimulation in both cell types. Gelsolin is an essential effector of rac-mediated actin dynamics, acting downstream of rac recruitment to the membrane.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: T
authors.initials: T
authors.lastname: Azuma
authors.forename: W
authors.initials: W
authors.lastname: Witke
authors.forename: T P
authors.initials: TP
authors.lastname: Stossel
authors.forename: J H
authors.initials: JH
authors.lastname: Hartwig
authors.forename: D J
authors.initials: DJ
authors.lastname: Kwiatkowski
mesh_terms: D000199:Actins / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000502:physiology; D002462:Cell Membrane; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology*; D019204:GTP-Binding Proteins / Q000032:analysis / Q000502:physiology*; D018260:Gelsolin / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011554:Pseudopodia; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000166:cytology; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins
chemical_list: D000199:Actins; D018797:Cell Cycle Proteins; D018260:Gelsolin; D004815:Epidermal Growth Factor; D019204:GTP-Binding Proteins; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D001920:Bradykinin