Regulation of Myosin Light Chain Function by BMP Signaling Controls Actin Cytoskeleton Remodeling

Cellular Physiology and Biochemistry

关键词: Cytoskeleton;    Myosin light chain;    Myosin light chain kinase;    Rho coiled-coiled kinase 1;    Transforming growth factor β;    Bone morphogenetic protein;    Actin;   

DOI  :  10.1159/000335790

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

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.

【 授权许可】

CC BY-NC-ND