title: RhoGDIβ Inhibits Bone Morphogenetic Protein 4 (BMP4)-induced Adipocyte Lineage Commitment and Favors Smooth Muscle-like Cell Differentiation.
abstract: The integration of signals involved in deciding the fate of mesenchymal stem cells is largely unknown. We used proteomics profiling to identify RhoGDIβ, an inhibitor of the small G-protein Rho family, as a component that regulates commitment of C3H10T1/2 mesenchymal stem cells to the adipocyte or smooth muscle cell lineage in response to bone morphogenetic protein 4 (BMP4). RhoGDIβ is notably down-regulated during BMP4-induced adipocytic lineage commitment of C3H10T1/2 mesenchymal stem cells, and this involves the cytoskeleton-associated protein lysyl oxidase. Excess RhoGDIβ completely prevents BMP4-induced commitment to the adipocyte lineage and simultaneously stimulates smooth muscle cell commitment by suppressing the activation of Rac1. Overexpression of RhoGDIβ induces stress fibers of F-actin by a process involving phosphomyosin light chain, indicating that cytoskeletal tension regulated by RhoGDIβ contributes to determining adipocyte versus myocyte commitment. Furthermore, the overexpression of RacV12 (constitutively active form of Rac1) totally rescues the inhibition of adipocyte commitment by RhoGDIβ, simultaneously preventing formation of the smooth muscle-like phenotype and disrupting the stress fibers in cells overexpressing RhoGDIβ. Collectively, these results indicate that RhoGDIβ functions as a novel BMP4 signaling target that regulates adipogenesis and myogensis.
authors.affiliation: From the Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032 and haiyanhuang@shmu.edu.cn.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Huang
authors.affiliation: From the Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032 and.
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Zhang
authors.affiliation: From the Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032 and.
authors.forename: Wen-Yan
authors.initials: WY
authors.lastname: Jiang
authors.affiliation: From the Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032 and.
authors.forename: Su-Zhen
authors.initials: SZ
authors.lastname: Chen
authors.affiliation: From the Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032 and.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: From the Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032 and.
authors.forename: Xin
authors.initials: X
authors.lastname: Ge
authors.affiliation: From the Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032 and.
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.affiliation: From the Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032 and.
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Dang
authors.affiliation: From the Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032 and.
authors.forename: Bo
authors.initials: B
authors.lastname: Wen
authors.affiliation: the Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, People's Republic of China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Liu
authors.affiliation: the Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, People's Republic of China.
authors.forename: Hao-Jie
authors.initials: HJ
authors.lastname: Lu
authors.affiliation: From the Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032 and qqtang@shmu.edu.cn.
authors.forename: Qi-Qun
authors.initials: QQ
authors.lastname: Tang
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D051379:Mice; D024510:Muscle Development / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D022502:Stress Fibers / Q000235:genetics / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta / Q000235:genetics / Q000378:metabolism*
chemical_list: C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D009479:Neuropeptides; C484602:Rac1 protein, mouse; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D020830:rac1 GTP-Binding Protein
keywords: Adipocyte; BMP4; Cytoskeleton; Lysyl Oxidase; Mesenchymal Stem Cells (MSCs); Ras-related C3 Botulinum Toxin Substrate 1 (Rac1); RhoGDIβ; Smooth Muscle-like Cells