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Publication : Homer modulates NFAT-dependent signaling during muscle differentiation.

First Author  Stiber JA Year  2005
Journal  Dev Biol Volume  287
Issue  2 Pages  213-24
PubMed ID  16226241 Mgi Jnum  J:103540
Mgi Id  MGI:3610274 Doi  10.1016/j.ydbio.2005.06.030
Citation  Stiber JA, et al. (2005) Homer modulates NFAT-dependent signaling during muscle differentiation. Dev Biol 287(2):213-24
abstractText  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.
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