Title
Opposing calcium-dependent signalling pathways control skeletal muscle differentiation by regulating a chromatin remodelling enzyme
UMMS Affiliation
Department of Cell and Developmental Biology; Proteomics and Mass Spectrometry Facility; Department of Biochemistry and Molecular Pharmacology
Publication Date
2015-06-17
Document Type
Article
Disciplines
Cell Biology | Computational Biology | Developmental Biology
Abstract
Calcium signalling is important for differentiation-dependent gene expression, but is also involved in other cellular functions. Therefore, mechanisms must exist to distinguish calcium signalling relevant to differentiation. Calcineurin is a calcium-regulated phosphatase that is required for myogenic gene expression and skeletal muscle differentiation. Here, we demonstrate that inhibition of calcineurin blocks chromatin remodelling and that the Brg1 ATPase of the SWI/SNF chromatin remodelling enzyme, which is required for the activation of myogenic gene expression, is a calcineurin substrate. Furthermore, we identify the calcium-regulated classical protein kinase C beta (PKCbeta) as a repressor of myogenesis and as the enzyme that opposes calcineurin function. Replacement of endogenous Brg1 with a phosphomimetic mutant in primary myoblasts inhibits myogenesis, whereas replacement with a non-phosphorylatable mutant allows myogenesis despite inhibition of calcineurin signalling, demonstrating the functionality of calcineurin/PKC-modified residues. Thus, the Brg1 chromatin remodelling enzyme integrates two antagonistic calcium-dependent signalling pathways that control myogenic differentiation.
Keywords
Biological sciences, Cell biology, Developmental biology
DOI of Published Version
10.1038/ncomms8441
Source
Nat Commun. 2015 Jun 17;6:7441. doi: 10.1038/ncomms8441. Link to article on publisher's site
Journal/Book/Conference Title
Nature communications
Related Resources
PubMed ID
26081415
Repository Citation
Nasipak BT, Padilla-Benavides T, Green KM, Leszyk JD, Mao W, Konda S, Sif S, Shaffer SA, Ohkawa Y, Imbalzano AN. (2015). Opposing calcium-dependent signalling pathways control skeletal muscle differentiation by regulating a chromatin remodelling enzyme. Cell and Developmental Biology Publications. https://doi.org/10.1038/ncomms8441. Retrieved from https://escholarship.umassmed.edu/cellbiology_pp/168