Functional Equivalence of Creatine Kinase Isoforms in Mouse Skeletal Muscle*
- From the ‡Department of Biological Sciences and Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213 and the§Department of Cell Biology and Histology, University of Nijmegen, P. O. Box 9101, 6500 AB Nijmegen, The Netherlands
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.
Footnotes
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↵* This work was supported by Grant-in-Aid 94017810 from the American Heart Association with funds contributed in part by the Pennsylvania Affiliate of the American Heart Association, by a National Institutes of Health Research Career Development Award 5 K04 HL-02847, by National Institutes of Health Grant R01-HL40354 (to A. P. K.), and by a National Institutes of Health National Research Service Award F32-HL08985 (to B. B. R.). The Pittsburgh NMR Center for Biomedical Research is supported by National Institutes of Health Grant RR-03631.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵¶ To whom correspondence should be addressed: Dept. of Biological Sciences, Carnegie Mellon University, 4400 Fifth Ave., Pittsburgh, PA 15213. Tel.: 412-268-5104; Fax: 412-268-7083; E-mail:ak5d{at}andrew.cmu.edu.
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↵1 The abbreviations used are: CK, creatine kinase; PCr, phosphocreatine; MM-CK, muscle isoenzyme of CK; BB-CK, brain isoform of CK; B-CK, B subunit of CK; M-CK, M subunit of CK; M-CK KO, mice that lack M-CK subunits due to gene disruption.
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- Received April 1, 1997.
- Revision received May 7, 1997.
