Remodeling muscles with calcineurin.
Ca(2+) signaling plays a central role in hypertrophic growth of cardiac and skeletal muscle in response to mechanical load and a variety of signals. However, the mechanisms whereby alterations in Ca(2+) in the cytoplasm activate the hypertrophic response and result in longterm changes in muscle gene expression are unclear. The Ca(2+), calmodulin-dependent protein phosphatase calcineurin has been proposed to control cardiac and skeletal muscle hypertrophy by acting as a Ca(2+) sensor that couples prolonged changes in Ca(2+) levels to reprogramming of muscle gene expression. Calcineurin also controls the contractile and metabolic properties of skeletal muscle by activating the slow muscle fiber-specific gene program, which is dependent on Ca(2+) signaling. Transcription factors of the NFAT and MEF2 families serve as endpoints for the signaling pathways whereby calcineurin controls muscle hypertrophy and fiber-type. We consider these findings in the context of a model for Ca(2+)-regulated gene expression in muscle cells and discuss potential implications of these findings for pharmacologic modification of cardiac and skeletal muscle function. BioEssays 22:510-519, 2000.
Olson
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EN
Department of Molecular Biology, University of Texas, Southwestern Medical Center at Dallas, Texas. eolson@hamon.swmed.edu
Williams
R S
RS
D000818:Animals; D019703:Calcineurin / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000209:etiology / Q000503:physiopathology; D004268:DNA-Binding Proteins / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D006984:Hypertrophy; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D009132:Muscles / Q000473:pathology* / Q000503:physiopathology*; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D012038:Regeneration; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology
D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D019703:Calcineurin; D002118:Calcium