Stem cell antigen-1 localizes to lipid microdomains and associates with insulin degrading enzyme in skeletal myoblasts

Conrad L. Epting, Frank W. King, Anissa Pedersen, Jessica Zaman, Carissa Ritner, Harold S. Bernstein

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Stem cell antigen-1 (Sca-1, Ly6A/E) is a glycosylphosphotidylinositol- anchored protein that identifies many tissue progenitor cells. We originally identified Sca-1 as a marker of myogenic precursor cells and subsequently demonstrated that Sca-1 regulates proliferation of activated myoblasts, suggesting an important role for Sca-1 in skeletal muscle homeostasis. Beyond its functional role in regulating proliferation, however, little is known about the mechanism(s) that drive Sca-1-mediated events. We now report that lipid microdomain organization is essential for normal myogenic differentiation, and that Sca-1 constitutively localizes to these domains during myoblast proliferation and differentiation. We also demonstrate that Sca-1 associates with insulin degrading enzyme (IDE), a catalytic protein responsible for the cleavage of mitogenic peptides, in differentiating myoblasts. We show that chemical inhibition of IDE as well as RNAi knockdown of IDE mRNA recapitulates the phenotype of Sca-1 interference, that is, sustained myoblast proliferation and delayed myogenic differentiation. These findings identify the first signaling protein that physically and functionally associates with Sca-1 in myogenic precursor cells, and suggest a potential pathway for Sca-1-mediated signaling. Future efforts to manipulate this pathway may lead to new strategies for augmenting the myogenic proliferative response, and ultimately muscle repair.

Original languageEnglish (US)
Pages (from-to)250-260
Number of pages11
JournalJournal of Cellular Physiology
Volume217
Issue number1
DOIs
StatePublished - Oct 2008

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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