Protein kinase C activity regulates slow myosin heavy chain 2 gene expression in slow lineage skeletal muscle fibers.
Expression of the slow myosin heavy chain (MyHC) 2 gene defines slow versus fast avian skeletal muscle fiber types. Fetal, or secondary, skeletal muscle fibers express slow MyHC isoform genes in developmentally regulated patterns within the embryo, and this patterning is at least partly dependent on innervation in vivo. We have previously shown that slow MyHC 2 gene expression in vitro is regulated by a combination of innervation and cell lineage. This pattern of gene expression was indistinguishable from the pattern observed in vivo in that it was restricted to innervated muscle fibers of slow muscle origin. We show here that slow MyHC 2 gene expression in the slow muscle fiber lineage is regulated by protein kinase C (PKC) activity. Inhibition of PKC activity induced slow MyHC 2 gene expression, and the capacity to express the slow MyHC 2 gene was restricted to muscle fibers of slow muscle (medial adductor) origin. Fast muscle fibers derived from the pectoralis major did not express significant levels of slow MyHC 2 with or without inhibitors of PKC activity. This differential expression pattern coincided with different inherent PKC activities in fast versus slow muscle fiber types. Furthermore, over-expression of an unregulated PKCalpha mutant suppressed slow MyHC 2 gene expression in muscle fibers of the slow lineage. Lastly, denervation of skeletal muscles caused an increase in PKC activity, particularly in the slow medial adductor muscle. This increase in PKC activity was associated with lack of slow MyHC 2 gene expression in vivo. These results provide a mechanistic link between innervation, an intracellular signaling pathway mediated by PKC, and expression of a muscle fiber type-specific contractile protein gene. Dev Dyn 1999;216:177-189.
DiMario
J X
JX
Department of Cell Biology and Anatomy, The Chicago Medical School, North Chicago, Illinois 60064, USA. dimarioj@finchcms.edu
Funk
P E
PE
D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D003472:Curare / Q000494:pharmacology; D003714:Denervation; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D018656:Muscle Fibers, Fast-Twitch / Q000201:enzymology; D018657:Muscle Fibers, Slow-Twitch / Q000201:enzymology*; D018482:Muscle, Skeletal / Q000196:embryology* / Q000201:enzymology; D018995:Myosin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D019311:Staurosporine / Q000494:pharmacology
D007211:Indoles; D008301:Maleimides; D003472:Curare; D011493:Protein Kinase C; D018995:Myosin Heavy Chains; D019311:Staurosporine; C088060:bisindolylmaleimide