Sarcoglycan Isoforms in Skeletal Muscle*
- From the ‡Burnham Institute, La Jolla, California 92037 and the §Department of Developmental Biology, Wenner-Gren Institute, Stockholm University, S-10691 Stockholm, Sweden
Abstract
The heterotetrameric sarcoglycan complex, composed of α-, β-, γ-, and δ-sarcoglycans, is an important component of the dystrophin-associated glycoprotein assembly in striated muscle. Mutations in any of the four genes encoding sarcoglycans cause a deficiency in all sarcoglycans in the sarcolemma and produce one of four types of limb-girdle muscular dystrophy. A fifth widely expressed sarcoglycan, ε-sarcoglycan, has been recently described. ε-Sarcoglycan is homologous to α-sarcoglycan, but whether it associates with the other sarcoglycans in muscle is not known. In this study, we use wild type and α-sarcoglycan-deficient mice to analyze the localization and association of sarcoglycans in skeletal muscle in vivo. The amounts of β-, γ-, and δ-sarcoglycans are reduced in α-sarcoglycan mutants, whereas the amount of ε-sarcoglycan is unchanged. We show here that ε-sarcoglycan is complexed with β-, γ-, and δ-sarcoglycans in both wild type and α-sarcoglycan mutant mice. We also use C2C12 myocytes to study the temporal expression and organization of sarcoglycan complexes during muscle cell differentiation in vitro. In C2C12 cells, α- and ε-sarcoglycans form separate complexes with β-, γ-, and δ-sarcoglycans. Both types of complexes are expressed at the cell surface and presumed to be functional. These results suggest that ε-sarcoglycan serves a function similar to that of α-sarcoglycan and that residual β-, γ-, and δ-sarcoglycan seen in mutant mice and α-sarcoglycan-deficient patients is due to its association with ε-sarcoglycan.
Footnotes
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↵* This work was supported in part by grants from the National Institutes of Health and 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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↵¶ To whom correspondence should be addressed: Burnham Inst., 10901 N. Torrey Pines Rd., La Jolla, CA 92037. Tel.: 858-646-3100; Fax: 858-646-3199; E-mail: eengvall@burnham.org.
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↵2 H. Baribault and M. Andahazy, unpublished data.
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↵3 L. A. Liu and E. Engvall, unpublished observations.
- Abbreviations:
- DAGC
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dystrophin-associated glycoprotein complex
- SGC
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sarcoglycan complex
- RT
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reverse transcription
- PCR
-
polymerase chain reaction
- kb
-
kilobase pair(s)
- PBS
-
phosphate-buffered saline
- PAGE
-
polyacrylamide gel electrophoresis
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- Received October 6, 1999.
- The American Society for Biochemistry and Molecular Biology, Inc.
