ε-Sarcoglycan Replaces α-Sarcoglycan in Smooth Muscle to Form a Unique Dystrophin-Glycoprotein Complex*
- Volker Straub‡§,
- Audrey J. Ettinger¶,
- Madeleine Durbeej‡‖,
- David P. Venzke‡,
- Susan Cutshall‡,
- Joshua R. Sanes¶ and
- Kevin P. Campbell‡**
- From the ‡Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242 and the¶Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110
Abstract
The sarcoglycan complex has been well characterized in striated muscle, and defects in its components are associated with muscular dystrophy and cardiomyopathy. Here, we have characterized the smooth muscle sarcoglycan complex. By examination of embryonic muscle lineages and biochemical fractionation studies, we demonstrated that ε-sarcoglycan is an integral component of the smooth muscle sarcoglycan complex along with β- and δ-sarcoglycan. Analysis of genetically defined animal models for muscular dystrophy supported this conclusion. The δ-sarcoglycan-deficient cardiomyopathic hamster and mice deficient in both dystrophin and utrophin showed loss of the smooth muscle sarcoglycan complex, whereas the complex was unaffected in α-sarcoglycan null mice in agreement with the finding that α-sarcoglycan is not expressed in smooth muscle cells. In the cardiomyopathic hamster, the smooth muscle sarcoglycan complex, containing ε-sarcoglycan, was fully restored following intramuscular injection of recombinant δ-sarcoglycan adenovirus. Together, these results demonstrate a tissue-dependent variation in the sarcoglycan complex and show that ε-sarcoglycan replaces α-sarcoglycan as an integral component of the smooth muscle dystrophin-glycoprotein complex. Our results also suggest a molecular basis for possible differential smooth muscle dysfunction in sarcoglycan-deficient patients.
Footnotes
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↵* This work was supported in part by grants from the Muscular Dystrophy Association (to K. P. C. and J. R. S.) and the National Institutes of Health (to J. R. S.).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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↵§ Supported by Grant Str 498/1-1 from the Deutsche Forschungsgemeinschaft.
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↵‖ Supported by the Swedish Foundation for International Cooperation in Research and Higher Education (STINT).
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↵** Investigator of the Howard Hughes Medical Institute. To whom correspondence should be addressed: Howard Hughes Medical Inst., University of Iowa College of Medicine, 400 EMRB, Iowa City, IA 52242. Tel.: 319-335-7867; Fax: 319-335-6957; E-mail: kevin-campbell@uiowa.edu.
- Abbreviations:
- DGC
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dystrophin-glycoprotein complex
- BSA
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bovine serum albumin
- PBS
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phosphate-buffered saline
- PAGE
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polyacrylamide gel electrophoresis
- E
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embryonal day
- P
-
postnatal day
- WGA. wheat germ agglutinin
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DEAE, diethylaminoethyl
- LGMD
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limb-girdle muscular dystrophy
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- Received June 2, 1999.
- Revision received July 6, 1999.
- The American Society for Biochemistry and Molecular Biology, Inc.
