MEF2 responds to multiple calcium-regulated signals in the control of skeletal muscle fiber type.

Published

Journal Article

Different patterns of motor nerve activity drive distinctive programs of gene transcription in skeletal muscles, thereby establishing a high degree of metabolic and physiological specialization among myofiber subtypes. Recently, we proposed that the influence of motor nerve activity on skeletal muscle fiber type is transduced to the relevant genes by calcineurin, which controls the functional activity of NFAT (nuclear family of activated T cell) proteins. Here we demonstrate that calcineurin-dependent gene regulation in skeletal myocytes is mediated also by MEF2 transcription factors, and is integrated with additional calcium-regulated signaling inputs, specifically calmodulin-dependent protein kinase activity. In skeletal muscles of transgenic mice, both NFAT and MEF2 binding sites are necessary for properly regulated function of a slow fiber-specific enhancer, and either forced expression of activated calcineurin or motor nerve stimulation up-regulates a MEF2-dependent reporter gene. These results provide new insights into the molecular mechanisms by which specialized characteristics of skeletal myofiber subtypes are established and maintained.

Full Text

Duke Authors

Cited Authors

  • Wu, H; Naya, FJ; McKinsey, TA; Mercer, B; Shelton, JM; Chin, ER; Simard, AR; Michel, RN; Bassel-Duby, R; Olson, EN; Williams, RS

Published Date

  • May 2000

Published In

Volume / Issue

  • 19 / 9

Start / End Page

  • 1963 - 1973

PubMed ID

  • 10790363

Pubmed Central ID

  • 10790363

Electronic International Standard Serial Number (EISSN)

  • 1460-2075

International Standard Serial Number (ISSN)

  • 0261-4189

Digital Object Identifier (DOI)

  • 10.1093/emboj/19.9.1963

Language

  • eng