Does contractile Ca2+ control calcineurin-NFAT signaling and pathological hypertrophy in cardiac myocytes?
In noncontractile cells, a sustained increase in total cytoplasmic Ca(2+) concentration is typically needed to activate the intracellular protein phosphatase calcineurin, leading to dephosphorylation of the transcription factor nuclear factor of activated T cells (NFAT), its nuclear translocation, and induction of gene expression. It remains a mystery exactly how Ca(2+)-dependent signaling pathways, such as that mediated by calcineurin-NFAT, are regulated in contracting cardiac myocytes given the highly specialized manner in which Ca(2+) concentration rhythmically cycles in excitation-contraction coupling. Here, we critically review evidence that supports the hypothesis that calcineurin-NFAT signaling is regulated by contractile Ca(2+) transients in cardiac myocytes.
Houser
Steven R
SR
Department of Physiology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140, USA. srhouser@temple.edu
Molkentin
Jeffery D
JD
D019703:Calcineurin / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D006332:Cardiomegaly / Q000473:pathology* / Q000503:physiopathology; D006333:Heart Failure / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008870:Microtubules / Q000502:physiology; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000473:pathology* / Q000502:physiology*; D050778:NFATC Transcription Factors / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000737:chemistry / Q000502:physiology; D015398:Signal Transduction
D050778:NFATC Transcription Factors; D011943:Receptors, Adrenergic, beta; D019703:Calcineurin; D002118:Calcium