A role for nephrin, a renal protein, in vertebrate skeletal muscle cell fusion
| Autor: | Jeffrey R. Guyon, Raghu Kalluri, Genri Kawahara, Louis M. Kunkel, Regina L. Sohn, Emanuela Gussoni, Ping Huang, Matthew Mitchell |
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| Rok vydání: | 2009 |
| Předmět: |
MAPK/ERK pathway
medicine.medical_specialty Muscle Fibers Skeletal urologic and male genital diseases Cell Fusion Myoblasts Nephrin Mice Myoblast fusion Internal medicine medicine Animals Humans Myocyte Muscle Skeletal Zebrafish Myogenin Multidisciplinary biology urogenital system Myogenesis Membrane Proteins Skeletal muscle Biological Sciences musculoskeletal system biology.organism_classification Coculture Techniques Cell biology Endocrinology medicine.anatomical_structure biology.protein tissues |
| Zdroj: | Proceedings of the National Academy of Sciences. 106:9274-9279 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Skeletal muscle is formed via fusion of myoblasts, a well-studied process in Drosophila . In vertebrates however, this process is less well understood, and whether there is evolutionary conservation with the proteins studied in flies is under investigation. Sticks and stones (Sns) , a cell surface protein found on Drosophila myoblasts, has structural homology to nephrin. Nephrin is a protein expressed in kidney that is part of the filtration barrier formed by podocytes. No previous study has established any role for nephrin in skeletal muscle. We show, using two models, zebrafish and mice, that the absence of nephrin results in poorly developed muscles and incompletely fused myotubes, respectively. Although nephrin-knockout (nephrin KO ) myoblasts exhibit prolonged activation of MAPK/ERK pathway during myogenic differentiation, expression of myogenin does not seem to be altered. Nevertheless, MAPK pathway blockade does not rescue myoblast fusion. Co-cultures of unaffected human fetal myoblasts with nephrin KO myoblasts or myotubes restore the formation of mature myotubes; however, the contribution of nephrin KO myoblasts is minimal. These studies suggest that nephrin plays a role in secondary fusion of myoblasts into nascent myotubes, thus establishing a possible functional conservation with Drosophila Sns . |
| Databáze: | OpenAIRE |
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