RhoE controls myoblast alignment prior fusion through RhoA and ROCK
| Autor: | Sophie Charrasse, Anne Blangy, Cécile Gauthier-Rouvière, Jérôme Kucharczak, Mathieu Fortier, Franck Comunale |
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| Přispěvatelé: | Centre de recherche en Biologie Cellulaire (CRBM), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1) |
| Rok vydání: | 2008 |
| Předmět: |
MESH: Signal Transduction
Male rho GTP-Binding Proteins RHOA Muscle Fibers Skeletal MESH: GTPase-Activating Proteins MESH: Down-Regulation Cell Fusion Myoblasts Mice Myoblast fusion 0302 clinical medicine MESH: Up-Regulation Myocyte MESH: Animals rho-Associated Kinases 0303 health sciences Myogenesis MESH: Muscle Fibers GTPase-Activating Proteins Cell Differentiation musculoskeletal system Up-Regulation Cell biology medicine.anatomical_structure 030220 oncology & carcinogenesis MESH: rho-Associated Kinases Signal transduction tissues C2C12 Signal Transduction MESH: Cell Differentiation MESH: rhoA GTP-Binding Protein MESH: Microscopy Electron Scanning Down-Regulation Biology Cell Line 03 medical and health sciences Downregulation and upregulation MESH: Mice Inbred C57BL medicine MESH: Cell Shape Animals [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology MESH: Myoblasts MESH: Mice Cell Shape Molecular Biology 030304 developmental biology Skeletal muscle Cell Biology MESH: rho GTP-Binding Proteins MESH: Male MESH: Cell Line Mice Inbred C57BL MESH: Cell Fusion Microscopy Electron Scanning biology.protein rhoA GTP-Binding Protein |
| Zdroj: | Cell Death and Differentiation Cell Death and Differentiation, Nature Publishing Group, 2008, 15 (8), pp.1221-31. ⟨10.1038/cdd.2008.34⟩ |
| ISSN: | 1476-5403 1350-9047 |
| DOI: | 10.1038/cdd.2008.34 |
| Popis: | International audience; Differentiation of skeletal myoblasts into multinucleated myotubes is a multi-step process orchestrated by several signaling pathways. The Rho small G protein family plays critical roles both during myogenesis induction and myoblast fusion. We report here that in C2C12 myoblasts, expression of RhoE, an atypical member of this family, increases until the onset of myoblast fusion before resuming its basal level once fusion has occurred. We show that RhoE accumulates in elongated, aligned myoblasts prior to fusion and that its expression is also increased during injury-induced skeletal muscle regeneration. Moreover, although RhoE is not required for myogenesis induction, it is essential for myoblast elongation and alignment before fusion and for M-cadherin expression and accumulation at the cell-cell contact sites. Myoblasts lacking RhoE present with defective p190RhoGAP activation and RhoA inhibition at the onset of myoblast fusion. RhoE interacts also with the RhoA effector Rho-associated kinase (ROCK)I whose activity must be downregulated to allow myoblast fusion. Consistently, we show that pharmacological inactivation of RhoA or ROCK restores myoblast fusion in RhoE-deficient myoblasts. RhoE physiological upregulation before myoblast fusion is responsible for the decrease in RhoA and ROCKI activities, which are required for the fusion process. Therefore, we conclude that RhoE is an essential regulator of myoblast fusion. |
| Databáze: | OpenAIRE |
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