title: Functional equivalence of creatine kinase isoforms in mouse skeletal muscle.
abstract: Creatine kinase (CK) is a highly conserved enzyme abundant in skeletal muscle that has a key role in high energy phosphate metabolism. The localization of the muscle isoenzyme of CK (MM-CK) to the M line and the sarcoplasmic reticulum of myofibrils has been suggested to be important for proper force development in skeletal muscle. The importance of this subcellular compartmentation has not been directly tested in vivo. To test the role of myofibrilar localization of CK, the consequences of a complete CK isoform switch from MM-CK to the brain (BB-CK) isoform, which does not localize to the M line, was studied in transgenic mouse skeletal muscle. In MM-CK knockout mice there are large contractile defects. When MM-CK was replaced by BB-CK, the aberrant contractile phenotypes seen in MM-CK knockout mice were returned to normal despite the lack of myofibrillar localization. These results indicate that CK compartmentation to the myofibril of skeletal muscle is not essential for contractile function and that there is functional equivalence of creatine kinase isoforms in supporting cellular energy metabolism.
authors.affiliation: Department of Biological Sciences and Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: B B
authors.initials: BB
authors.lastname: Roman
authors.forename: B
authors.initials: B
authors.lastname: Wieringa
authors.forename: A P
authors.initials: AP
authors.lastname: Koretsky
mesh_terms: D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism*; D004734:Energy Metabolism; D007527:Isoenzymes; D051379:Mice; D009119:Muscle Contraction; D018485:Muscle Fibers, Skeletal / Q000201:enzymology; D018482:Muscle, Skeletal / Q000201:enzymology*
chemical_list: D007527:Isoenzymes; D003402:Creatine Kinase