Homer modulates NFAT-dependent signaling during muscle differentiation.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Stiber, JA; Tabatabaei, N; Hawkins, AF; Hawke, T; Worley, PF; Williams, RS; Rosenberg, P

Published Date

  • November 15, 2005

Published In

Volume / Issue

  • 287 / 2

Start / End Page

  • 213 - 224

PubMed ID

  • 16226241

International Standard Serial Number (ISSN)

  • 0012-1606

Digital Object Identifier (DOI)

  • 10.1016/j.ydbio.2005.06.030


  • eng

Conference Location

  • United States