Show simple item record

dc.contributor.authorKalluri, Raghu
dc.contributor.authorGussoni, Emanuela
dc.contributor.authorKunkel, Louis M.
dc.contributor.authorGuyon, Jeffrey
dc.contributor.authorMitchell, Matthew
dc.contributor.authorKawahara, Genri
dc.contributor.authorHuang, Ping
dc.contributor.authorSohn, Regina Lee
dc.date.accessioned2010-03-12T19:21:07Z
dc.date.available2010-03-12T19:21:07Z
dc.date.issued2009-04
dc.date.submitted2009-02
dc.identifier.issn1091-6490
dc.identifier.issn0027-8424
dc.identifier.urihttp://hdl.handle.net/1721.1/52549
dc.description.abstractSkeletal 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.en
dc.description.sponsorshipNational Institute of Health (5P30HD018655)en
dc.language.isoen_US
dc.publisherUnited States National Academy of Sciencesen
dc.relation.isversionofhttp://dx.doi.org/10.1073/pnas.0904398106en
dc.rightsArticle 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.en
dc.sourcePNASen
dc.titleA role for nephrin, a renal protein, in vertebrate skeletal muscle cell fusionen
dc.typeArticleen
dc.identifier.citationSohn, 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 Sciencesen
dc.contributor.departmentHarvard University--MIT Division of Health Sciences and Technologyen_US
dc.contributor.approverKalluri, Raghu
dc.contributor.mitauthorKalluri, Raghu
dc.relation.journalProceedings of the National Academy of Sciences of the United States of Americaen
dc.eprint.versionFinal published versionen
dc.type.urihttp://purl.org/eprint/type/JournalArticleen
eprint.statushttp://purl.org/eprint/status/PeerRevieweden
dspace.orderedauthorsSohn, R. L.; Huang, P.; Kawahara, G.; Mitchell, M.; Guyon, J.; Kalluri, R.; Kunkel, L. M.; Gussoni, E.en
mit.licensePUBLISHER_POLICYen
mit.metadata.statusComplete


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record