Assembly of the Sarcoglycan Complex
INSIGHTS FOR MUSCULAR DYSTROPHY*
- From the Howard Hughes Medical Institute, Department of Physiology and Biophysics, and Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242
Abstract
Four unique transmembrane glycoproteins comprise the sarcoglycan complex in striated muscle. The sarcoglycan complex contributes to maintenance of sarcolemma integrity. A shared feature of four types of autosomal recessive limb girdle muscular dystrophy (LGMD) is that mutations in a single sarcoglycan gene result in the loss of all sarcoglycans at the sarcolemma. The mechanism of destabilization is unknown. We report here our findings of sarcoglycan complex biosynthesis in a heterologous cell system. We demonstrate that the sarcoglycans are glycosylated and assemble into a complex that resides in the plasma membrane. Complex assembly was dependent on the simultaneous synthesis of all four sarcoglycans. Mutant sarcoglycans block complex formation and insertion of the sarcoglycans into the plasma membrane. This constitutes the first biochemical evidence to support the idea that the molecular defect in sarcoglycan-deficient LGMD is because of aberrant sarcoglycan complex assembly and trafficking, which leads to the absence of the complex from the sarcolemma.
Footnotes
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↵* This research was supported in part by the Muscular Dystrophy Association.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 the University of Iowa Diabetes and Endocrinology Research Center.
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↵§ Investigator of the Howard Hughes Medical Institute. To whom correspondence and requests for materials 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{at}uiowa.edu.
- Abbreviations:
- DGC
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dystrophin-glycoprotein complex
- SG
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sarcoglycan
- LGMD
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limb girdle muscular dystrophy
- CFTR
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cystic fibrosis transmembrane conductance regulator
- CF
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cystic fibrosis
- CHO
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Chinese hamster ovary
- PBS
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phosphate-buffered saline.
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- Received August 18, 1998.
- Revision received October 9, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
