Skip to main content

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

Publication ,  Journal Article
Wu, H; Naya, FJ; McKinsey, TA; Mercer, B; Shelton, JM; Chin, ER; Simard, AR; Michel, RN; Bassel-Duby, R; Olson, EN; Williams, RS
Published in: EMBO J
May 2, 2000

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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

EMBO J

DOI

ISSN

0261-4189

Publication Date

May 2, 2000

Volume

19

Issue

9

Start / End Page

1963 / 1973

Location

England

Related Subject Headings

  • Transcriptional Activation
  • Transcription Factors
  • Protein Binding
  • Phosphorylation
  • Organ Specificity
  • Nuclear Proteins
  • NFATC Transcription Factors
  • Myogenic Regulatory Factors
  • Muscle, Skeletal
  • Muscle Fibers, Slow-Twitch
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wu, H., Naya, F. J., McKinsey, T. A., Mercer, B., Shelton, J. M., Chin, E. R., … Williams, R. S. (2000). MEF2 responds to multiple calcium-regulated signals in the control of skeletal muscle fiber type. EMBO J, 19(9), 1963–1973. https://doi.org/10.1093/emboj/19.9.1963
Wu, H., F. J. Naya, T. A. McKinsey, B. Mercer, J. M. Shelton, E. R. Chin, A. R. Simard, et al. “MEF2 responds to multiple calcium-regulated signals in the control of skeletal muscle fiber type.EMBO J 19, no. 9 (May 2, 2000): 1963–73. https://doi.org/10.1093/emboj/19.9.1963.
Wu H, Naya FJ, McKinsey TA, Mercer B, Shelton JM, Chin ER, et al. MEF2 responds to multiple calcium-regulated signals in the control of skeletal muscle fiber type. EMBO J. 2000 May 2;19(9):1963–73.
Wu, H., et al. “MEF2 responds to multiple calcium-regulated signals in the control of skeletal muscle fiber type.EMBO J, vol. 19, no. 9, May 2000, pp. 1963–73. Pubmed, doi:10.1093/emboj/19.9.1963.
Wu H, Naya FJ, McKinsey TA, Mercer B, Shelton JM, Chin ER, Simard AR, Michel RN, Bassel-Duby R, Olson EN, Williams RS. MEF2 responds to multiple calcium-regulated signals in the control of skeletal muscle fiber type. EMBO J. 2000 May 2;19(9):1963–1973.

Published In

EMBO J

DOI

ISSN

0261-4189

Publication Date

May 2, 2000

Volume

19

Issue

9

Start / End Page

1963 / 1973

Location

England

Related Subject Headings

  • Transcriptional Activation
  • Transcription Factors
  • Protein Binding
  • Phosphorylation
  • Organ Specificity
  • Nuclear Proteins
  • NFATC Transcription Factors
  • Myogenic Regulatory Factors
  • Muscle, Skeletal
  • Muscle Fibers, Slow-Twitch