BACKGROUND/AIMS: Actin cytoskeleton dynamics support and coordinate signaling events that control cell proliferation, differentiation and migration. Growth factors provide essential signals that act on multi-protein complexes that regulate actin assembly with myosin. We previously analyzed the action of the transforming growth factor β (TGF-β) and now extend our studies to the bone morphogenetic protein (BMP) 7, an important regulator of stem cell function and bone differentiation. METHODS: Using a well-established cell model of actin dynamics, Swiss3T3 fibroblasts, we applied cell biological and biochemical approaches to monitor the pathway that links the BMP-7 receptors to the acto-myosin complex. RESULTS: We demonstrate that BMP-7 induces actin and focal adhesion remodeling in starved fibroblasts as potently as TGF-β. BMP-7 mediates changes of actin dynamics via the kinase ROCK1 and induces rapid activation of RhoA and RhoB with concomitant inactivation of Cdc42. These molecular events correlate well with induction of phosphorylation on Ser19 of the myosin light chain, but not with LIMK1 kinase activation. Depletion of endogenous myosin light chain inhibits actin remodeling induced by BMP-7. This novel pathway regulates fibroblast migration without affecting cell proliferation. CONCLUSION: We establish a BMP-Rho-ROCK1 pathway, which targets myosin light chain to control actin remodeling in fibroblasts.
BACKGROUND/AIMS: Actin cytoskeleton dynamics support and coordinate signaling events that control cell proliferation, differentiation and migration. Growth factors provide essential signals that act on multi-protein complexes that regulate actin assembly with myosin. We previously analyzed the action of the transforming growth factor β (TGF-β) and now extend our studies to the bone morphogenetic protein (BMP) 7, an important regulator of stem cell function and bone differentiation. METHODS: Using a well-established cell model of actin dynamics, Swiss3T3 fibroblasts, we applied cell biological and biochemical approaches to monitor the pathway that links the BMP-7 receptors to the acto-myosin complex. RESULTS: We demonstrate that BMP-7 induces actin and focal adhesion remodeling in starved fibroblasts as potently as TGF-β. BMP-7 mediates changes of actin dynamics via the kinase ROCK1 and induces rapid activation of RhoA and RhoB with concomitant inactivation of Cdc42. These molecular events correlate well with induction of phosphorylation on Ser19 of the myosin light chain, but not with LIMK1 kinase activation. Depletion of endogenous myosin light chain inhibits actin remodeling induced by BMP-7. This novel pathway regulates fibroblast migration without affecting cell proliferation. CONCLUSION: We establish a BMP-Rho-ROCK1 pathway, which targets myosin light chain to control actin remodeling in fibroblasts.
Authors: Megha Talati; James West; Rinat Zaynagetdinov; Charles C Hong; Wei Han; Tom Blackwell; Linda Robinson; Timothy S Blackwell; Kirk Lane Journal: PLoS One Date: 2014-04-08 Impact factor: 3.240
Authors: Sabyasachi Dasgupta; Thorsten Auth; Nir S Gov; Timothy J Satchwell; Eric Hanssen; Elizabeth S Zuccala; David T Riglar; Ashley M Toye; Timo Betz; Jake Baum; Gerhard Gompper Journal: Biophys J Date: 2014-07-01 Impact factor: 4.033