A 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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| Format: | Article |
| Language: | en_US |
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United States National Academy of Sciences
2010
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| Online Access: | http://hdl.handle.net/1721.1/52549 |
| _version_ | 1826196134521995264 |
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| author | Kalluri, Raghu Gussoni, Emanuela Kunkel, Louis M. Guyon, Jeffrey Mitchell, Matthew Kawahara, Genri Huang, Ping Sohn, Regina Lee |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Kalluri, Raghu Gussoni, Emanuela Kunkel, Louis M. Guyon, Jeffrey Mitchell, Matthew Kawahara, Genri Huang, Ping Sohn, Regina Lee |
| author_sort | Kalluri, Raghu |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T10:21:22Z |
| format | Article |
| id | mit-1721.1/52549 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:21:22Z |
| publishDate | 2010 |
| publisher | United States National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/525492022-09-30T20:36:03Z A role for nephrin, a renal protein, in vertebrate skeletal muscle cell fusion Kalluri, Raghu Gussoni, Emanuela Kunkel, Louis M. Guyon, Jeffrey Mitchell, Matthew Kawahara, Genri Huang, Ping Sohn, Regina Lee Harvard University--MIT Division of Health Sciences and Technology Kalluri, Raghu Kalluri, Raghu 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. National Institute of Health (5P30HD018655) 2010-03-12T19:21:07Z 2010-03-12T19:21:07Z 2009-04 2009-02 Article http://purl.org/eprint/type/JournalArticle 1091-6490 0027-8424 http://hdl.handle.net/1721.1/52549 Sohn, Regina Lee et al. “A role for nephrin, a renal protein, in vertebrate skeletal muscle cell fusion.” Proceedings of the National Academy of Sciences 106.23 (2009): 9274-9279. © 2010 National Academy of Sciences en_US http://dx.doi.org/10.1073/pnas.0904398106 Proceedings of the National Academy of Sciences of the United States of America Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf United States National Academy of Sciences PNAS |
| spellingShingle | Kalluri, Raghu Gussoni, Emanuela Kunkel, Louis M. Guyon, Jeffrey Mitchell, Matthew Kawahara, Genri Huang, Ping Sohn, Regina Lee A role for nephrin, a renal protein, in vertebrate skeletal muscle cell fusion |
| title | A role for nephrin, a renal protein, in vertebrate skeletal muscle cell fusion |
| title_full | A role for nephrin, a renal protein, in vertebrate skeletal muscle cell fusion |
| title_fullStr | A role for nephrin, a renal protein, in vertebrate skeletal muscle cell fusion |
| title_full_unstemmed | A role for nephrin, a renal protein, in vertebrate skeletal muscle cell fusion |
| title_short | A role for nephrin, a renal protein, in vertebrate skeletal muscle cell fusion |
| title_sort | role for nephrin a renal protein in vertebrate skeletal muscle cell fusion |
| url | http://hdl.handle.net/1721.1/52549 |
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