| First Author | Chen J | Year | 2006 |
| Journal | Exp Cell Res | Volume | 312 |
| Issue | 9 | Pages | 1610-25 |
| PubMed ID | 16524571 | Mgi Jnum | J:111508 |
| Mgi Id | MGI:3654235 | Doi | 10.1016/j.yexcr.2006.01.024 |
| Citation | Chen J, et al. (2006) Identification of functional domains in sarcoglycans essential for their interaction and plasma membrane targeting. Exp Cell Res 312(9):1610-25 |
| abstractText | 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. |
