Myoferlin regulation by NFAT in muscle injury, regeneration and repair

Alexis R. Demonbreun, Karen A. Lapidos, Konstantina Heretis, Samantha Levin, Rodney Dale, Peter Pytel, Eric C. Svensson, Elizabeth M. McNally

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Ferlin proteins mediate membrane-fusion events in response to Ca 2+. Myoferlin, a member of the ferlin family, is required for normal muscle development, during which it mediates myoblast fusion. We isolated both damaged and intact myofibers from a mouse model of muscular dystrophy using laser-capture microdissection and found that the levels of myoferlin mRNA and protein were increased in damaged myofibers. To better define the components of the muscle-injury response, we identified a discreet 1543-bp fragment of the myoferlin promoter, containing multiple NFAT-binding sites, and found that this was sufficient to drive high-level myoferlin expression in cells and in vivo. This promoter recapitulated normal myoferlin expression in that it was downregulated in healthy myofibers and was upregulated in response to myofiber damage. Transgenic mice expressing GFP under the control of the myoferlin promoter were generated and GFP expression in this model was used to track muscle damage in vivo after muscle injury and in muscle disease. Myoferlin modulates the response to muscle injury through its activity in both myoblasts and mature myofibers.

Original languageEnglish (US)
Pages (from-to)2413-2422
Number of pages10
JournalJournal of cell science
Volume123
Issue number14
DOIs
StatePublished - Jul 15 2010

Keywords

  • Muscle regeneration
  • Myoblast
  • Myoferlin
  • Myofiber
  • NFAT

ASJC Scopus subject areas

  • Cell Biology

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    Demonbreun, A. R., Lapidos, K. A., Heretis, K., Levin, S., Dale, R., Pytel, P., Svensson, E. C., & McNally, E. M. (2010). Myoferlin regulation by NFAT in muscle injury, regeneration and repair. Journal of cell science, 123(14), 2413-2422. https://doi.org/10.1242/jcs.065375