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Assessment of the contribution of various Ca 2+ /Calcineurin‐regulated NFAT isoforms to the process of skeletal muscle fiber remodelling
Author(s) -
Eibl Joe Karl,
Michel Stephanie,
Pavlath Grace K.,
Michel Robin N.
Publication year - 2007
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.21.6.a1207-a
Subject(s) - nfat , calcineurin , gene isoform , transcription factor , phenotype , microbiology and biotechnology , skeletal muscle , colocalization , biology , chemistry , medicine , endocrinology , biochemistry , gene , transplantation
Calcineurin (Cn) is a Ca 2+ ‐regulated serine/threonine phosphatase that acts on the Nuclear Factor of Activated T‐cells (NFAT) family of transcription factors. Involvement of the Cn/NFAT signaling pathway in the modulation of the skeletal muscle fiber phenotype is recognized, however, the role of the various Cn‐regulated NFAT isoforms (NFATc1‐c3) in this modulation is still emerging. We thus assessed the expression and function of each NFAT factor in muscle fibers from wild type or transgenic NFATc2‐ or NFATc3‐deficient mice under normal weightbearing or functional work overload conditions. Using immunofluorescent nuclear colocalization assays and RT‐PCR analysis, we show that normal weight bearing mice harbouring mutant NFAT isoforms display compensatory increases of surviving NFAT family members that may act as surrogates to maintain a semblance of the original muscle phenotype. On the other hand, when muscles of NFAT mutant mice were functionally overloaded the phenotype remodeling associated with this model was differentially prevented suggesting distinct roles for NFATc1‐c3 in response to various functional challenges. (Funded by NSERC, CIHR and CRC to RNM)