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A role for nephrin, a renal protein, in vertebrate skeletal muscle cell fusion.

ABSTRACT: 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.

SUBMITTER: Sohn RL

PROVIDER: S-EPMC2695070 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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A role for nephrin, a renal protein, in vertebrate skeletal muscle cell fusion.

Sohn Regina Lee RL Huang Ping P Kawahara Genri G Mitchell Matthew M Guyon Jeffrey J Kalluri Raghu R Kunkel Louis M LM Gussoni Emanuela E

Proceedings of the National Academy of Sciences of the United States of America 20090522 23

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 estab ...[more]

PMID: 19470472

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Dataset Information

A role for nephrin, a renal protein, in vertebrate skeletal muscle cell fusion.

Publications

A role for nephrin, a renal protein, in vertebrate skeletal muscle cell fusion.

Similar Datasets

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