Homer modulates NFAT-dependent signaling during muscle differentiation

Jonathan A. Stiber, Niloufar Tabatabaei, April F. Hawkins, Thomas Hawke, Paul F. Worley, R. Sanders Williams, Paul Rosenberg

Research output: Contribution to journalArticle

Abstract

While changes in intracellular calcium are well known to influence muscle contraction through excitation contraction coupling, little is understood of the calcium signaling events regulating gene expression through the calcineurin/NFAT pathway in muscle. Here, we demonstrate that Ca+2 released via the inositol trisphosphate receptor (IP3R) increases nuclear entry of NFAT in undifferentiated skeletal myoblasts, but the IP3R Ca+2 pool in differentiated myotubes promotes nuclear exit of NFAT despite a comparable quantitative change in [Ca+2]i. In contrast, Ca+2 released via ryanodine receptors (RYR) increases NFAT nuclear entry in myotubes. The scaffolding protein Homer, known to interact with both IP3R and RYR, is expressed as part of the myogenic differentiation program and enhances NFAT-dependent signaling by increasing RYR Ca+2 release. These results demonstrate that differentiated skeletal myotubes employ discrete pools of intracellular calcium to restrain (IP3R pool) or activate (RYR pool) NFAT-dependent signaling, in a manner distinct from undifferentiated myoblasts. The selective expression of Homer proteins contributes to these differentiation-dependent features of calcium signaling.

Original languageEnglish (US)
Pages (from-to)213-224
Number of pages12
JournalDevelopmental biology
Volume287
Issue number2
DOIs
StatePublished - Nov 15 2005

Keywords

  • Calcineurin
  • Calcium
  • Myogenesis
  • Scaffolds
  • Transcription

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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  • Cite this

    Stiber, J. A., Tabatabaei, N., Hawkins, A. F., Hawke, T., Worley, P. F., Williams, R. S., & Rosenberg, P. (2005). Homer modulates NFAT-dependent signaling during muscle differentiation. Developmental biology, 287(2), 213-224. https://doi.org/10.1016/j.ydbio.2005.06.030