RhoGDIß Inhibits Bone Morphogenetic Protein 4 (BMP4)-induced Adipocyte Lineage Commitment and Favors Smooth Muscle-like Cell Differentiation.

Huang, Hai-Yan; Zhang, Wen-Ting; Jiang, Wen-Yan; Chen, Su-Zhen; Liu, Yang; Ge, Xin; Li, Xi; Dang, Yong-Jun; Wen, Bo; Liu, Xiao-Hui; Lu, Hao-Jie; Tang, Qi-Qun

Huang, Hai-Yan; Zhang, Wen-Ting; Jiang, Wen-Yan; Chen, Su-Zhen; Liu, Yang; Ge, Xin; Li, Xi; Dang, Yong-Jun; Wen, Bo; Liu, Xiao-Hui; Lu, Hao-Jie; Tang, Qi-Qun.

Afiliación

Huang HY; 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.
Zhang WT; 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.
Jiang WY; 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.
Chen SZ; 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.
Liu Y; 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.
Ge X; 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.
Li X; 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.
Dang YJ; 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.
Wen B; 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.
Liu XH; the Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, People's Republic of China.
Lu HJ; the Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, People's Republic of China.
Tang QQ; 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.

J Biol Chem ; 290(17): 11119-29, 2015 Apr 24.

Article en En | MEDLINE | ID: mdl-25778399

RESUMEN

The integration of signals involved in deciding the fate of mesenchymal stem cells is largely unknown. We used proteomics profiling to identify RhoGDIß, 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). RhoGDIß 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 RhoGDIß completely prevents BMP4-induced commitment to the adipocyte lineage and simultaneously stimulates smooth muscle cell commitment by suppressing the activation of Rac1. Overexpression of RhoGDIß induces stress fibers of F-actin by a process involving phosphomyosin light chain, indicating that cytoskeletal tension regulated by RhoGDIß 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 RhoGDIß, simultaneously preventing formation of the smooth muscle-like phenotype and disrupting the stress fibers in cells overexpressing RhoGDIß. Collectively, these results indicate that RhoGDIß functions as a novel BMP4 signaling target that regulates adipogenesis and myogensis.

Asunto(s)

Adipocitos/metabolismo; Proteína Morfogenética Ósea 4/metabolismo; Diferenciación Celular/fisiología; Desarrollo de Músculos/fisiología; Miocitos del Músculo Liso/metabolismo; Transducción de Señal/fisiología; Inhibidor beta de Disociación del Nucleótido Guanina rho/metabolismo; Adipocitos/citología; Animales; Proteína Morfogenética Ósea 4/genética; Línea Celular; Ratones; Miocitos del Músculo Liso/citología; Neuropéptidos/genética; Neuropéptidos/metabolismo; Fibras de Estrés/genética; Fibras de Estrés/metabolismo; Proteína de Unión al GTP rac1/genética; Proteína de Unión al GTP rac1/metabolismo; Inhibidor beta de Disociación del Nucleótido Guanina rho/genética

Palabras clave

Adipocyte; BMP4; Cytoskeleton; Lysyl Oxidase; Mesenchymal Stem Cells (MSCs); Ras-related C3 Botulinum Toxin Substrate 1 (Rac1); RhoGDIß; Smooth Muscle-like Cells

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Diferenciación Celular / Adipocitos / Desarrollo de Músculos / Miocitos del Músculo Liso / Proteína Morfogenética Ósea 4 / Inhibidor beta de Disociación del Nucleótido Guanina rho Límite: Animals Idioma: En Revista: J Biol Chem Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos

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