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

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 pro...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2009-06, Vol.106 (23), p.9274-9279
Main Authors: Sohn, Regina Lee, Huang, Ping, Kawahara, Genri, Mitchell, Matthew, Guyon, Jeffrey, Kalluri, Raghu, Kunkel, Louis M, Gussoni, Emanuela
Format: Article
Language:English
Subjects:
Animals
Biological Sciences
Cell Fusion
Coculture Techniques
Cultured cells
Danio rerio
Drosophila
Embryos
Gene expression
Humans
Insects
Kidneys
Membrane Proteins - metabolism
Mice
Muscle fibers
Muscle Fibers, Skeletal - metabolism
Muscle, Skeletal - cytology
Muscle, Skeletal - metabolism
Muscles
Musculoskeletal system
Myoblasts
Myoblasts - metabolism
Proteins
Skeletal muscle
Skeletal muscle satellite cells
Studies
Vertebrates
Zebrafish
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Summary: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 (nephrinKO) 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 nephrinKO myoblasts or myotubes restore the formation of mature myotubes; however, the contribution of nephrinKO 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0904398106