Identification of Functional Domains in Sarcoglycans Essential for Their Interaction and Plasma Membrane Targeting.
From: Sigfried and Janet Weis Center for Research, M.C. 26-11, the Geisinger Clinic, 100 North Academy Avenue, Danville, PA 17822, USA.
Experimental cell research
- Publish Date: May 2006
- ISSN: 0014-4827
- Volume: 312
- Issue: 9
- Pages: 1610-25
- Medium: Print
- Language: English
- Citation (JAMA): Chen Jiwei, Shi Weixing, Zhang Yuguang, et al. Identification of Functional Domains in Sarcoglycans Essential for Their Interaction and Plasma Membrane Targeting.. Exp. Cell Res. May 2006;312:1610-25
Abstract
Mutations in sarcoglycans have been reported to cause autosomal-recessive limb-girdle muscular dystrophies. In skeletal and cardiac muscle, sarcoglycans are assembled into a complex on the sarcolemma from four subunits (alpha, beta, gamma, delta). In this report, we present a detailed structural analysis of sarcoglycans using deletion study, limited proteolysis and co-immunoprecipitation. Our results indicate that the extracellular regions of sarcoglycans consist of distinctive functional domains connected by proteinase K-sensitive sites. The N-terminal half domains are required for sarcoglycan interaction. The C-terminal half domains of beta-, gamma- and delta-sarcoglycan consist of a cysteine-rich motif and a previously unrecognized conserved sequence, both of which are essential for plasma membrane localization. Using a heterologous expression system, we demonstrate that missense sarcoglycan mutations affect sarcoglycan complex assembly and/or localization to the cell surface. Our data suggest that the formation of a stable complex is necessary but not sufficient for plasma membrane targeting. Finally, we provide evidence that the beta/delta-sarcoglycan core can associate with the C-terminus of dystrophin. Our results therefore generate important information on the structure of the sarcoglycan complex and the molecular mechanisms underlying the effects of various sarcoglycan mutations in muscular dystrophies.
Mesh Headings (Keywords): Amino Acid Sequence, Animals, Binding Sites, COS Cells, Cell Membrane, Cercopithecus aethiops, Cysteine, Dystrophin, Glycosylation, Immunoprecipitation, Mice, Models, Molecular, Molecular Sequence Data, Mutation, Protein Binding, Protein Subunits, Protein Transport, Rats, Sarcoglycans, Sequence Homology, Amino Acid, Transfection
Check for Full Text / PubMed Unique Identifier (PMID): 16524571
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