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Altered calcineurin‐NFAT signaling in the hearts of NFATc2 null mice
Author(s) -
SinChan Patrick,
Michel Robin N.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb595
Subject(s) - nfat , calcineurin , transcription factor , gene isoform , microbiology and biotechnology , biology , genetics , medicine , gene , transplantation
The Ca 2+ ‐ dependent phosphatase, calcineurin, and its downstream transcriptional effectors, nuclear factor of activated T‐cells (NFAT), are major intracellular modulators of cardiac hypertrophy. Transcription factor NFATc2 has recently been identified as the major NFAT isoform responsible for calcineurin‐mediated cardiac hypertrophy. We thus investigated the role of each NFAT isoform (c1–c4), the NFATc2 binding partner GATA‐4, and NFAT/GATA‐4 kinases in regulating the cardiac phenotype by assessing their expression at the transcript and protein levels in NFATc2 −/− mice. Cardiac mRNA and protein expressions of other members of the NFAT family were similar in wild type and NFATc2−/− mice, suggesting that individual NFAT isoforms are independently regulated. Expression of cytoplasmic GATA‐4 was unchanged whereas nuclear GATA‐4 was higher in hearts from NFATc2 −/− mice, indicating increased nuclear transit of this transcription factor in the absence of NFATc2. In support of this, the expression of MAPK, responsible for GATA‐4 DNA binding ability, remained unchanged whereas GSK3‐β, which promotes GATA‐4 nuclear export, was lower in NFATc2 −/− hearts. Taken together, our data identify molecular partners that may compensate for the lack of NFATc2, thereby providing further insight towards understanding calcineurin‐mediated cardiomyopathy. Supported by CIHR, NSERC and CRC to RNM.