Calcineurin-mediated signaling in skeletal muscle

Abstract

Calcineurin (Cn; protein phosphatase 2B) is a calcium-activated phosphatase that is highly conserved among eukaryotes. Calcineurin dephosphorylates a wide variety of substrates making it a versatile second messenger for intracellular calcium signals in many tissues. In muscle, Cn transduces signals that determine fiber type, hypertrophy, and commitment to the myogenic lineage. Calcineurin-mediated fiber transitions of fast to slow involve the nucleocytoplasmic shuttling of the transcription factor, NFAT. Less is known about the Cn-mediated signaling pathways that promote muscle hypertrophy and expression of the fast phenotype, although they are undoubtedly intertwined with a variety of other signaling pathways. This paper reviews Cn-dependent signaling in muscle with special emphasis on the role of Cn in mediating fiber type transitions and muscle hypertrophy. To open the door on the role and extent of Cn-mediated signaling in livestock, evidence is presented that in callipyge lambs Cn actively mediates muscle hypertrophy in a fiber type-specific manner. Increased understanding of Cn-dependent signaling in livestock will enhance our ability to control and select for extent of muscling and meat quality attributes. Key words: Calcineurin, signal transduction, muscle, review