Trends in Pharmacological Sciences
ReviewCalcineurin signaling and neural control of skeletal muscle fiber type and size
Section snippets
Muscle fiber type plasticity
Based on the particular isoform of myosin heavy chain (MyHC) that they express, mammalian skeletal muscles comprise slow (type 1) and fast (type 2) fibers; the latter can be further subdivided into three subsets: type 2A, 2X (also called 2D) and 2B [2]. Intermediate fiber types with mixed MyHC composition (e.g. 1+2A, 2A+2X and 2X+2B) are also present in most skeletal muscles, giving rise to a continuous spectrum of fiber types: 1 ↔ 2A ↔ 2X ↔ 2B. These fibers also differ in oxidative enzyme and
Calcineurin signaling
Calcineurin, a serine/threonine phosphatase consisting of a catalytic (calcineurin A) and a regulatory (calcineurin B) subunit, is a major mediator of Ca2+ signaling in different cell systems. Both calcineurin A and B subunits comprise several isoforms coded by different genes or generated by alternative splicing. When activated by Ca2+–calmodulin binding, calcineurin affects gene expression by dephosphorylating specific substrates, including the four calcineurin-dependent members of the
Concluding remarks
Multiple signaling pathways control fiber size and fiber type in skeletal muscle. Calcineurin signaling is involved in the nerve-activity-dependent induction and maintenance of fiber-type-specific gene programs. NFATs are good candidates for transcriptional effectors of calcineurin activation, as shown by the finding that the nuclear translocation of NFATc1 is responsive to specific patterns of electrical stimuli known to affect the fast and slow phenotype. By contrast, calcineurin does not
Acknowledgements
We apologize to our colleagues whose work was not directly cited in this review owing to space limitations. Work in our laboratory is supported by the Italian Ministry of Education, University and Research, the Italian Space Agency, the European Commission (contract QLK6–2000–00530) and the Giovanni Armenise-Harvard Foundation for Advanced Scientific Research. We thank Jesper L. Andersen for Fig. 1.
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