Human Molecular Genetics, 2002, Vol. 11, No. 18 2147-2154
© 2002 Oxford University Press
-Sarcoglycan, a novel component of the sarcoglycan complex, is reduced in muscular dystrophy
1Department of Molecular Genetics and Cell Biology, 2Department of Medicine, Section of Cardiology and 3Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA
Received May 3, 2002; Revised June 26, 2002; Accepted June 28, 2002
DDBJ/EMBL/GenBank accession no. AY095374
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONRESULTSDISCUSSIONMATERIALS AND METHODSREFERENCES |
|---|
The dystrophin glycoprotein complex (DGC) is found at the plasma membrane of muscle cells, where it provides a link between the cytoskeleton and the extracellular matrix. A subcomplex within the DGC, the sarcoglycan complex, associates with dystrophin and mediates muscle membrane stability. Mutations in sarcoglycan genes lead to muscular dystrophy and cardiomyopathy in both humans and mice. In invertebrates, there are three sarcoglycan genes, while in mammals there are additional sarcoglycan genes that probably arose from gene duplication events. We identified a novel mammalian sarcoglycan,
-sarcoglycan, that is highly related to 
-sarcoglycan and 
-sarcoglycan. We generated a -sarcoglycan-specific antibody and found that -sarcoglycan associated with other members of the sarcoglycan complex at the plasma membrane. Additionally, -sarcoglycan was reduced at the membrane in muscular dystrophy, consistent with a role in mediating membrane stability. -Sarcoglycan was also found as a component of the vascular smooth muscle sarcoglycan complex. Together, these data demonstrate that -sarcoglycan is an integral component of the sarcoglycan complex and, as such, is important in the pathogenesis of muscular dystrophy. |
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONRESULTSDISCUSSIONMATERIALS AND METHODSREFERENCES |
|---|
The dystrophin glycoprotein complex (DGC) is a membrane-spanning complex that links the interior cytoskeleton to the extracellular matrix in muscle (1). Dystrophin, a spectrin repeat-containing protein, links cytoplasmic actin filaments to the plasma membrane through dystroglycan. Mutations in the dystrophin gene produce Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). The sarcoglycan complex is a subcomplex within the DGC and is composed of several muscle-specific, transmembrane proteins (
-, ß-, - and -sarcoglycan) (2). Mutations in these sarcoglycan genes lead to limb girdle muscular dystrophy type 2 (LGMD) (3–8). Both DMD/BMD and the LGMDs are characterized by dissolution of the sarcoglycan complex and muscle membrane instability. In the muscular dystrophies, muscle membrane instability leads to increased intracellular calcium and myofiber degeneration. A fifth sarcoglycan subunit, 
-sarcoglycan, is more broadly expressed (9,10). In humans, mutations in the -sarcoglycan gene are associated with myoclonus–dystonia syndrome (11). Additional members of the DGC, such as the syntrophins and the dystrobrevins, appear to stabilize protein–protein interactions within the DGC (12).
The sarcoglycans are asparagine-linked glycosylated proteins with single transmembrane domains (13). The sarcoglycan complex requires coordinated translation and assembly of its subunits for maintenance in the muscle membrane (2,14,15). Murine models of sarcoglycan mutations have been generated and recapitulate the human muscular dystrophy phenotype (2,15–19). Additionally, ß-, - or -sarcoglycan mutant mice, as well as the hamster model of -sarcoglycan deficiency, the BIO14.6 Syrian cardiomyopathic hamster, show evidence of cardiomyocyte damage and cardiac disease, emphasizing the role of the sarcoglycan complex in the heart (20).
Analysis of invertebrate genomes reveals only three sarcoglycan genes (21). Drosophila has three sarcoglycan genes: one homologous to mammalian - and -sarcoglycan, a second homologous to ß-sarcoglycan, and a third homologous to - and -sarcoglycans (21). In mammals, -sarcoglycan and -sarcoglycan appear to have arisen from a gene duplication event (8,10). Similarly, -sarcoglycan and -sarcoglycan have an identical intron–exon gene structure consistent with gene duplication (22,23). Thus, mammals may have diversified sarcoglycan subtypes concomitant with muscle specialization to accommodate the needs of striated and smooth muscle. Although the precise function of sarcoglycan is not known, sarcoglycan has both mechanical and non-mechanical roles that mediate interactions between the extracellular matrix, the membrane and the cytoskeleton (24).
We now report -sarcoglycan, a protein highly related to -sarcoglycan and -sarcoglycan, encoded by a gene on human chromosome 8. An antibody specific to -sarcoglycan was used to demonstrate that -sarcoglycan was expressed in muscle and co-immunoprecipitated with other sarcoglycan components. Moreover, -sarcoglycan was reduced in muscle with sarcoglycan gene mutations. Together, these data identify -sarcoglycan as a candidate gene for muscular dystrophy and a potential mediator of muscle membrane instability in DGC-mediated muscular dystrophy.
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONRESULTSDISCUSSIONMATERIALS AND METHODSREFERENCES |
|---|
-sarcoglycan is highly related to -sarcoglycan and -sarcoglycanThrough electronic database searches and RT–PCR, we identified murine
-sarcoglycan (Fig. 1). Murine -sarcoglycan is 89% identical at the nucleotide level to human -sarcoglycan (GenBank accession number AY028700). Human -sarcoglycan genomic sequences revealed an identical intron–exon structure to that of -sarcoglycan and -sarcoglycan (22,23). The human -sarcoglycan gene was found on chromosome 8p22.
|
Mouse
-sarcoglycan was compared to the amino acid sequences of mouse -sarcoglycan and -sarcoglycan (Fig. 1). -Sarcoglycan shared 57% and 55.7% amino acid identity and 74.8% and 74.2% similarity with -sarcoglycan and -sarcoglycan, respectively. -Sarcoglycan was substantially less homologous to ß-sarcoglycan (21.4% identical and 38.7% similar). The single //-sarcoglycan-like genes in C. elegans and Drosophila melanogaster were equally related to murine -, - or -sarcoglycan. There is an alternative translation start site for -sarcoglycan within exon 1 that would add the residues MDRSTDLDIQELK at the N-terminus. These additional residues have homologous sequences in Drosophila //-sarcoglycan. The single transmembrane domain found in -sarcoglycan is consistent with a cytoplasmic N-terminus similar to -sarcoglycan and -sarcoglycan. The putative asparagine glycosylation site, at amino acid 110 (108 in -sarcoglycan), is conserved among -, - and -sarcoglycans. At the C-terminus are four conserved cysteines that form intramolecular disulfide bonds (25). Based on human muscular dystrophy mutation data, these conserved cysteines are important in the production of a functional protein (3,4,26,27).
To study -sarcoglycan, we generated a -sarcoglycan-specific antibody (ZSG1). Because of the high degree of homology among -, - and -sarcoglycans, we chose a region of -sarcoglycan in the putative intracellular domain (Fig. 1, highlighted region). Figure 2 demonstrates that ZSG1 was highly specific for -sarcoglycan and did not cross-react with -sarcoglycan or -sarcoglycan. Immunoblotting with previously characterized antibodies to -sarcoglycan and -sarcoglycan (3,15) demonstrated that these antibodies are specific for - and -sarcoglycan, respectively, and do not cross-react with -sarcoglycan.
|
-Sarcoglycan is found in striated and vascular smooth muscleThe sarcoglycans are transmembrane proteins found in the plasma membrane of muscle cells.
-Sarcoglycan was similarly found in the membrane of skeletal and cardiac muscle (Fig. 3A and C–F). -Sarcoglycan colocalized with dystrophin (Fig. 3C). Both dystrophin and the sarcoglycan complex are concentrated at costameres, discrete subcellular structures that overlie Z-lines (28–30). -Sarcoglycan was also found in a costameric pattern (Fig. 3D). A variant of the sarcoglycan complex is found in vascular smooth muscle (31). We found that -sarcoglycan was expressed in the smooth muscle layer of coronary arteries, consistent with expression in vascular smooth muscle (Fig. 3E and F). Smooth muscle -actin costaining identified the smooth muscle layer (Fig. 3F). ZSG1 did not stain a thin layer of endothelial cells, indicating ZSG1 is specific to smooth muscle cells.
|
-Sarcoglycan expression in muscular dystrophyTargeted disruptions of murine
-sarcoglycan (gsg-/-) or -sarcoglycan (dsg-/-) produce muscular dystrophy similar to that in humans with LGMDs (15,17,19). In LGMD and DMD, disruption of the sarcoglycan complex occurs and is associated with abnormal membrane permeability and membrane instability (15,24,32). Using ZSG1, we tested heavy microsomal fractions from skeletal muscle from control, gsg-/- and dsg-/- tissue. Heavy microsomes from muscle include the sarcolemma and contain the sarcoglycan complex (33–36). -Sarcoglycan expression was slightly reduced in gsg-/- and greatly reduced in dsg-/- heavy microsomes when compared to control (Fig. 4A). These findings parallel the reduction of other sarcoglycans seen in gsg-/- and dsg-/- skeletal muscle microsomes (15). Additionally, microsomes from mdx mice, a naturally occurring model of dystrophin deficiency (37), showed reduced levels of -sarcoglycan (data not shown). Immunoprecipitation of heavy microsomes using a ß-sarcoglycan antibody demonstrated that -sarcoglycan bound the sarcoglycan complex (Fig. 4B) in control skeletal muscle membranes. Interestingly, this association was not significantly disrupted in sarcoglycan mutant microsomes. In addition, we performed immunoprecipitation with the ZSG1 antisera (Fig. 4C). We found that ZSG1 specifically precipitated dystrophin, indicating that it interacts with dystrophin. This interaction was not eliminated in gsg-/- and dsg-/- skeletal muscle microsomes, where dystrophin is normally present despite disruption of the sarcoglycan complex (15,19).
|
-Sarcoglycan expression in vascular smooth muscleThoracic aorta and the rat aorta smooth muscle cell line (A7r5) (38) were studied for
-sarcoglycan expression (Fig. 5A). Aorta from gsg-/- and dsg-/- muscle did not show a decrease of -sarcoglycan staining, suggesting that -sarcoglycan expression in vascular smooth muscle was not disrupted as it is in striated muscle. Using our sarcoglycan-specific antibodies, we determined that ß-sarcoglycan was normally present in aorta in both gsg-/- and dsg-/- samples and that -sarcoglycan was normally present in gsg-/- aorta (Fig. 5B). -Sarcoglycan was not detected in aorta but was readily observed in microsomes from control skeletal muscle. Moreover, -sarcoglycan associated with ß-sarcoglycan and -sarcoglycan in smooth muscle. Immunoprecipitation with a ß-sarcoglycan antibody showed that both -sarcoglycan and -sarcoglycan contribute to the smooth muscle sarcoglycan complex (Fig. 5C). Interestingly, in the smooth muscle cell line, A7r5, less -sarcoglycan was present (Fig. 5C), but normal levels of -sarcoglycan were not required for the association of ß-sarcoglycan with -sarcoglycan.
|
40 kDa. (B) Immunoblots from aorta express |
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONRESULTSDISCUSSIONMATERIALS AND METHODSREFERENCES |
|---|
An essential function of the DGC is to mediate interaction between extracellular matrix proteins, such as laminin, the membrane and cytoskeletal elements. Disruption of the DGC leads to membrane instability, membrane permeability defects and myofiber damage. Dystroglycan is a major transmembrane linker within the DGC, and binds laminin
2 (39). Dystroglycan is found on nearly all cell types and helps order the extracellular matrix in development (40). In contrast, the sarcoglycan complex is found exclusively in muscle, where it has been proposed to stabilize the interaction between - and ß-dystroglycan (32). The potential ligands for sarcoglycan in the extracellular matrix are unknown. On the cytoplasmic surface, -sarcoglycan and -sarcoglycan bind a muscle-specific form of filamin (41).
We have now identified the sixth member of the sarcoglycan complex, -sarcoglycan, and found that -sarcoglycan is highly related to -sarcoglycan and -sarcoglycan. Each of these genes is encoded by eight identically placed exons, consistent with preserved gene structure and multiple gene duplication events. The gene encoding -sarcoglycan is found on human chromosome 8p22. At this date, no neuromuscular disorders have been mapped to human chromosomal region 8p22, but the identification of the -sarcoglycan gene will facilitate its study in muscular dystrophy and other neuromuscular diseases.
Using a -sarcoglycan-specific antibody, we demonstrated that -sarcoglycan was expressed at the plasma membrane in muscle. -Sarcoglycan was expressed in heart, skeletal muscle and arterial vascular smooth muscle. Immunoprecipitation experiments showed an association of -sarcoglycan with ß-sarcoglycan. As ß-sarcoglycan is one of the earliest sarcoglycan proteins to assemble into the sarcoglycan complex (15), these data confirm that -sarcoglycan is an integral member of the sarcoglycan complex. The reduction of -sarcoglycan at the membrane in sarcoglycan mutant muscle is further evidence that -sarcoglycan interacts with the remainder of the sarcoglycan complex. Furthermore, -sarcoglycan is disrupted in genetically diverse forms of muscular dystrophy. Together, these findings identify -sarcoglycan as an integral component of the sarcoglycan complex.
It has been suggested that disruption of the vascular smooth muscle complex leads to primary vasospasm, thereby causing regional damage in sarcoglycan-deficient cardiac muscle (16,17). For these and other studies, the expression of sarcoglycan proteins in smooth muscle was studied using several different anti-sarcoglycan antibodies (31). Because of the increasing complexity of sarcoglycan sequences, previously generated antibodies against -sarcoglycan or -sarcoglycan may cross-react with -sarcoglycan. Now, using antibodies specific to -sarcoglycan, -sarcoglycan and -sarcoglycan, we have shown that only -sarcoglycan and -sarcoglycan are expressed in arterial vascular smooth muscle, while -sarcoglycan is not. Furthermore, the smooth muscle sarcoglycan complex is not disrupted in -sarcoglycan mutant aorta. The generation of sarcoglycan-specific antibodies, particularly those specific to -, - and -sarcoglycan, clarifies the composition of the vascular smooth muscle sarcoglycan complex. These data suggest that vasospasm, as it occurs in sarcoglycan-deficient muscle, may not be related to disruption of the vascular smooth muscle sarcoglycan complex. Further studies may clarify the roles of -, - and -sarcoglycan in all types of smooth muscle, including arterial vascular, gastrointestinal, genitourinary, bronchial and venous vascular smooth muscle.
-Sarcoglycan may be important for the maintenance of striated muscle membrane stability. Autosomal recessive mutations in -, ß-, - and -sarcoglycan lead to muscular dystrophy in humans and mice. Mutations in -sarcoglycan have been recently described as leading to the movement disorder myoclonus–dystonia. Loss of function, or disruption of the sarcoglycan complex in striated muscle, appears to be a critical element in the generation of the muscular dystrophy phenotype. The disruption of -sarcoglycan that occurs as a result of sarcoglycan or dystrophin mutations is a likely contributor to the underlying pathologic process in muscular dystrophy.
|
MATERIALS AND METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONRESULTSDISCUSSIONMATERIALS AND METHODSREFERENCES |
|---|
Isolation and characterization of
-sarcoglycan cDNAWhole RNA from mouse heart or skeletal muscle was prepared using the TRIzol reagent (Invitrogen, Carlsbad, USA) and reverse transcribed as described (42). Primers based on rat and mouse partial
-sarcoglycan expressed sequence tags (ESTs) (Accession numbers BG664629 and BB045304) were designed (mZSG1F 5'-ATGACTCGAGAACAATACATACTAGCCACACAGCA-3' and mZSG900R 5'-TCAGTTCCACAAGCAAATGCTACTACTGGACTGAC-3') and used to amplify the complete open reading frame of murine -sarcoglycan using LA-Taq (TaKaRa). The resulting product was ligated into pCRII-TOPO (Invitrogen) and cycle sequenced.
ZSG1 antibody production
An antibody specific to murine -sarcoglycan (ZSG1) was generated using the peptide CILATQQNNLPRPENAQLYP-COOH as an epitope (Zymed Laboratories, South San Francisco, CA, USA). Affinity-purified ZSG1 was prepared using immobilized peptide on a SulfoLink Column (Pierce, Rockford, IL, USA). Antisera were applied to the peptide column, eluted with 100 mM glycine, pH 2.0, and immediately neutralized with 1 M Tris base, pH 9.5. Affinity purified antibody was concentrated (Amicon, Beverly, MA, USA).
E.coli expression constructs and bacterial expression
The complete open reading frame of murine -sarcoglycan was ligated into a TAT-less pTAT vector (43) (kind gift from Dr Steve Dowdy, UCSD). Similar constructs were generated using the full-length murine -sarcoglycan (nucleotides 271–1140 of Genbank accession number AB024923) and -sarcoglycan (nucleotides 152–1027 of Genbank accession number AF282901) cDNAs and green fluorescent protein (GFP) cDNA (Clontech, Palo Alto, CA, USA). Each expression plasmid was transformed into BL21 (DE3) plysS cells. Bacterial cell pellets were resuspended in 8 M urea, 100 mM NaH2PO4, 10 mM Tris, pH 8.0. Protein content was quantified by BioRad (Hercules, CA, USA) protein assay.
Immunoblotting
Protein samples (35 µg) were separated on 10% polyacrylamide Tris–SDS gels in Tris–glycine, pH 7.4, and transferred to Immobilon-P PVDF (Millipore, Bedford, MA, USA). Blots were blocked with 5% non-fat dry milk in 150 mM NaCl, 50 mM Tris, pH 7.4, with 0.5% Tween-20 (TBS-T) and incubated with ZSG1 (1 : 1200), anti--sarcoglycan (1 : 3000) (15), anti--sarcoglycan (1 : 1000) (3) or anti-ß-sarcoglycan (1 : 2000) (44). Horse radish peroxidase (HRP)-conjugated goat anti-rabbit IgG (Jackson Immunoresearch, West Grove, PA, USA), ECL-Plus (Amersham Pharmacia Biotech, Piscataway, NJ, USA) and Biomax MS film (Eastman Kodak, Rochester, NY, USA) were used. Equal loading was confirmed by Coomassie staining of gels and/or Ponceau S staining of membranes.
Immunofluorescence microscopy
Heart and skeletal muscle from control mice were mounted in TissueTek (Miles, Elkhard, IN, USA) and frozen in liquid nitrogen-cooled isopentane. Cryosections (6–8 µm thickness) were prepared as described (3). Affinity-purified -sarcoglycan antibody (1 : 500), monoclonal ß-sarcoglycan antibody (1 : 200, NCL-BSG, Novocastra, Newcastle upon Tyne, UK), monoclonal anti-dystrophin antibody (1 : 200, NCL-Dys2, Novocastra) and monoclonal anti-smooth muscle -actin (1 : 400, clone 1A4, Sigma, St. Louis, MO, USA) antibody were used. Slides were incubated with Cy3-conjugated goat anti-rabbit antibody and fluorescein isothiocyanate (FITC)-conjugated goat anti-mouse antibody (Jackson Immunoresearch). Results were imaged on a Zeiss Axiophot using a Zeiss Axiocam (Carl Zeiss, Oberkochen, Germany).
Protein preparation
Whole hearts or thoracic aorta from the diaphragm to the level of the aortic arch were dissected from adult (3–7-month) control, gsg-/- (19) and dsg-/- (15) animals. The tissue was frozen in liquid nitrogen, powdered, resuspended in IP buffer [50 mM Tris–Cl, pH 7.4, 165 mM NaCl, 1 mM EGTA, 1 mM EDTA, 1% Triton X-100, 0.1% sodium dodecyl sulfate (SDS), 1% sodium deoxycholate, 1 mM sodium orthovanadate, 10 mM NaF, 10 mM sodium pyrophosphate, 1 mM phenylmethylsulfonyl fluoride (PMSF)] plus Complete Protease Inhibitor tablet (Roche, Mannheim, Germany) and incubated for 15' min on ice as described (45). Lysate was passed 10 times through a 25G needle. Sheared lysate was spun at 12 000 g for 15 min at 4°C. The rat aorta smooth muscle cell line A7r5 (38) (ATCC, Manassas, VA, USA) was grown in Dulbecco's modified Eagle's medium with 10% fetal bovine serum and 1% penicillin/streptomycin (Invitrogen) to confluence. Cells were rinsed, harvested and resuspended in lysis buffer (50 mM HEPES, pH 7.5, 150 mM NaCl, 2 mM EDTA, 10 mM NaF, 10 mM sodium pyrophosphate, 1 mM sodium orthovanadate, 10% glycerol, 1% Triton X-100) plus Complete Protease Inhibitor and 0.5 mM PMSF. After incubation on ice for 20 min, the lysate was centrifuged at 10 000 g for 5 min at 4°C. Supernatant protein content was quantified by BioRad protein assay.
Heavy microsome preparation from skeletal muscle and immunoprecipitation
Skeletal muscle microsome preparation was performed as described (15,33). Approximately 150 µg of skeletal muscle microsomes or 200 µg of aorta lysate was incubated with 50 µl protein G sepharose beads (Amersham) for 1 h at 4°C. Bead-cleared samples were incubated with 25 µl monoclonal ß-sarcoglycan antibody (NCL-BSG) or -sarcoglycan antisera (ZSG1) for 3 h at 4°C. One hundred microliters of beads were added and incubated for an additional hour. Immunocomplex-bound beads were collected and washed seven times with IP buffer, without SDS and sodium deoxycholate, on ice. Sample buffer was added and analyzed by immunoblotting as above.
|
ACKNOWLEDGEMENTS |
|---|
This work was supported by the NIH (HL61322), the Burroughs Wellcome Fund, the Muscular Dystrophy Association, and the American Heart Association (EMM). M.T.W. is supported by the Medical Scientist Training Program (NIH GM07281).
|
FOOTNOTES |
|---|
* To whom correspondence should be addressed at: University of Chicago, Section of Cardiology, 5841 S. Maryland, MC 6088, Chicago, IL 60637, USA. Tel: +1 7737022672; Fax: +1 7737022681; Email: emcnally{at}medicine.bsd.uchicago.edu
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONRESULTSDISCUSSIONMATERIALS AND METHODSREFERENCES |
|---|
1 Bonnemann, C.G., McNally, E.M. and Kunkel, L.M. (1996) Beyond dystrophin: current progress in the muscular dystrophies. Curr. Opin. Pediatr., 8, 569–582.[Medline]
2 Hack, A.A., Groh, M.E. and McNally, E.M. (2000) Sarcoglycans in muscular dystrophy. Microsc. Res. Tech., 48, 167–180.[Web of Science][Medline]
3
McNally, E.M., Duggan, D., Gorospe, J.R., Bonnemann, C.G., Fanin, M., Pegoraro, E., Lidov, H.G., Noguchi, S., Ozawa, E., Finkel, R.S. et al. (1996) Mutations that disrupt the carboxyl-terminus of gamma-sarcoglycan cause muscular dystrophy. Hum. Mol. Genet., 5, 1841–1847.
4 Nigro, V., de Sa Moreira, E., Piluso, G., Vainzof, M., Belsito, A., Politano, L., Puca, A.A., Passos-Bueno, M.R. and Zatz, M. (1996) Autosomal recessive limb-girdle muscular dystrophy, LGMD2F, is caused by a mutation in the delta-sarcoglycan gene. Nat. Genet., 14, 195–198.[Web of Science][Medline]
5 Bonnemann, C.G., Modi, R., Noguchi, S., Mizuno, Y., Yoshida, M., Gussoni, E., McNally, E.M., Duggan, D.J., Angelini, C. and Hoffman, E.P. (1995) Beta-sarcoglycan (A3b) mutations cause autosomal recessive muscular dystrophy with loss of the sarcoglycan complex. Nat. Genet., 11, 266–273.[Web of Science][Medline]
6
Noguchi, S., McNally, E.M., Ben Othmane, K., Hagiwara, Y., Mizuno, Y., Yoshida, M., Yamamoto, H., Bonnemann, C.G., Gussoni, E., Denton, P.H. et al. (1995) Mutations in the dystrophin-associated protein gamma-sarcoglycan in chromosome 13 muscular dystrophy. Science, 270, 819–822.
7 Lim, L.E., Duclos, F., Broux, O., Bourg, N., Sunada, Y., Allamand, V., Meyer, J., Richard, I., Moomaw, C., Slaughter, C. et al. (1995) Beta-sarcoglycan: characterization and role in limb-girdle muscular dystrophy linked to 4q12. Nat. Genet., 11, 257–265.[Web of Science][Medline]
8 Piccolo, F., Roberds, S.L., Jeanpierre, M., Leturcq, F., Azibi, K., Beldjord, C., Carrie, A., Recan, D., Chaouch, M., Reghis, A. et al. (1995) Primary adhalinopathy: a common cause of autosomal recessive muscular dystrophy of variable severity. Nat. Genet., 10, 243–245.[Web of Science][Medline]
9
Ettinger, A.J., Feng, G. and Sanes, J.R. (1997) epsilon-Sarcoglycan, a broadly expressed homologue of the gene mutated in limb-girdle muscular dystrophy 2D. J. Biol. Chem., 272, 32534–32538.
10 McNally, E.M., Ly, C.T. and Kunkel, L.M. (1998) Human epsilon-sarcoglycan is highly related to alpha-sarcoglycan (adhalin), the limb girdle muscular dystrophy 2D gene. FEBS Lett., 422, 27–32.[Web of Science][Medline]
11 Zimprich, A., Grabowski, M., Asmus, F., Naumann, M., Berg, D., Bertram, M., Scheidtmann, K., Kern, P., Winkelmann, J., Muller-Myhsok, B. et al. (2001) Mutations in the gene encoding epsilon-sarcoglycan cause myoclonus–dystonia syndrome. Nat. Genet., 29, 66–69.[Web of Science][Medline]
12
Yoshida, M., Hama, H., Ishikawa-Sakurai, M., Imamura, M., Mizuno, Y., Araishi, K., Wakabayashi-Takai, E., Noguchi, S., Sasaoka, T. and Ozawa, E. (2000) Biochemical evidence for association of dystrobrevin with the sarcoglycan–sarcospan complex as a basis for understanding sarcoglycanopathy. Hum. Mol. Genet., 9, 1033–1040.
13 Ozawa, E., Noguchi, S., Mizuno, Y., Hagiwara, Y. and Yoshida, M. (1998) From dystrophinopathy to sarcoglycanopathy: evolution of a concept of muscular dystrophy. Muscle Nerve, 21, 421–438.[Web of Science][Medline]
14
Holt, K.H. and Campbell, K.P. (1998) Assembly of the sarcoglycan complex. Insights for muscular dystrophy. J. Biol. Chem., 273, 34667–34670.
15 Hack, A.A., Lam, M.Y., Cordier, L., Shoturma, D.I., Ly, C.T., Hadhazy, M.A., Hadhazy, M.R., Sweeney, H.L. and McNally, E.M. (2000) Differential requirement for individual sarcoglycans and dystrophin in the assembly and function of the dystrophin–glycoprotein complex. J. Cell Sci., 113, 2535–2544.[Abstract]
16 Durbeej, M., Cohn, R.D., Hrstka, R.F., Moore, S.A., Allamand, V., Davidson, B.L., Williamson, R.A. and Campbell, K.P. (2000) Disruption of the beta-sarcoglycan gene reveals pathogenetic complexity of limb-girdle muscular dystrophy type 2E. Mol. Cell, 5, 141–151.[Web of Science][Medline]
17 Coral-Vazquez, R., Cohn, R.D., Moore, S.A., Hill, J.A., Weiss, R.M., Davisson, R.L., Straub, V., Barresi, R., Bansal, D., Hrstka, R.F. et al. (1999) Disruption of the sarcoglycan-sarcospan complex in vascular smooth muscle: a novel mechanism for cardiomyopathy and muscular dystrophy. Cell, 98, 465–474.[Web of Science][Medline]
18
Duclos, F., Straub, V., Moore, S.A., Venzke, D.P., Hrstka, R.F., Crosbie, R.H., Durbeej, M., Lebakken, C.S., Ettinger, A.J., van der Meulen, J. et al. (1998) Progressive muscular dystrophy in alpha-sarcoglycan-deficient mice. J. Cell Biol., 142, 1461–1471.
19
Hack, A.A., Ly, C.T., Jiang, F., Clendenin, C.J., Sigrist, K.S., Wollmann, R.L. and McNally, E.M. (1998) Gamma-sarcoglycan deficiency leads to muscle membrane defects and apoptosis independent of dystrophin. J. Cell Biol., 142, 1279–1287.
20 Heydemann, A., Wheeler, M.T. and McNally, E.M. (2001) Cardiomyopathy in animal models of muscular dystrophy. Curr. Opin. Cardiol., 16, 211–217.[Web of Science][Medline]
21 Greener, M.J. and Roberts, R.G. (2000) Conservation of components of the dystrophin complex in Drosophila. FEBS Lett., 482, 13–18.[Web of Science][Medline]
22
Nigro, V., Piluso, G., Belsito, A., Politano, L., Puca, A.A., Papparella, S., Rossi, E., Viglietto, G., Esposito, M.G., Abbondanza, C. et al. (1996) Identification of a novel sarcoglycan gene at 5q33 encoding a sarcolemmal 35 kDa glycoprotein. Hum. Mol. Genet., 5, 1179–1186.
23 McNally, E.M., Passos-Bueno, M.R., Bonnemann, C.G., Vainzof, M., de Sa Moreira, E., Lidov, H.G., Othmane, K.B., Denton, P.H., Vance, J.M., Zatz, M. et al. (1996) Mild and severe muscular dystrophy caused by a single gamma-sarcoglycan mutation. Am. J. Hum. Genet., 59, 1040–1047.[Web of Science][Medline]
24 Hack, A.A., Cordier, L., Shoturma, D.I., Lam, M.Y., Sweeney, H.L. and McNally, E.M. (1999) Muscle degeneration without mechanical injury in sarcoglycan deficiency. Proc. Natl Acad. Sci. USA, 96, 10723–10728.
25
Chan, Y.M., Bonnemann, C.G., Lidov, H.G. and Kunkel, L.M. (1998) Molecular organization of sarcoglycan complex in mouse myotubes in culture. J. Cell Biol., 143, 2033–2044.
26
Piccolo, F., Jeanpierre, M., Leturcq, F., Dode, C., Azibi, K., Toutain, A., Merlini, L., Jarre, L., Navarro, C., Krishnamoorthy, R. et al. (1996) A founder mutation in the gamma-sarcoglycan gene of gypsies possibly predating their migration out of India. Hum. Mol. Genet., 5, 2019–2022.
27
Moreira, E.S., Vainzof, M., Marie, S.K., Nigro, V., Zatz, M. and Passos-Bueno, M.R. (1998) A first missense mutation in the delta sarcoglycan gene associated with a severe phenotype and frequency of limb-girdle muscular dystrophy type 2F (LGMD2F) in Brazilian sarcoglycanopathies. J. Med. Genet., 35, 951–953.
28
Williams, M.W. and Bloch, R.J. (1999) Extensive but coordinated reorganization of the membrane skeleton in myofibers of dystrophic (mdx) mice. J. Cell Biol., 144, 1259–1270.
29
Rybakova, I.N., Patel, J.R. and Ervasti, J.M. (2000) The dystrophin complex forms a mechanically strong link between the sarcolemma and costameric actin. J. Cell Biol., 150, 1209–1214.
30 Gossrau, R. (1998) Nitric oxide synthase I (NOS I) is a costameric enzyme in rat skeletal muscle. Acta Histochem., 100, 451–462.[Web of Science][Medline]
31
Straub, V., Ettinger, A.J., Durbeej, M., Venzke, D.P., Cutshall, S., Sanes, J.R. and Campbell, K.P. (1999) epsilon-Sarcoglycan replaces alpha-sarcoglycan in smooth muscle to form a unique dystrophin–glycoprotein complex. J. Biol. Chem., 274, 27989–27996.
32
Straub, V., Duclos, F., Venzke, D.P., Lee, J.C., Cutshall, S., Leveille, C.J. and Campbell, K.P. (1998) Molecular pathogenesis of muscle degeneration in the delta-sarcoglycan-deficient hamster. Am. J. Pathol., 153, 1623–1630.
33
Ohlendieck, K., Ervasti, J.M., Snook, J.B. and Campbell, K.P. (1991) Dystrophin–glycoprotein complex is highly enriched in isolated skeletal muscle sarcolemma. J. Cell Biol., 112, 135–148.
34
Yoshida, M. and Ozawa, E. (1990) Glycoprotein complex anchoring dystrophin to sarcolemma. J. Biochem. (Tokyo), 108, 748–752.
35 Ervasti, J.M. and Campbell, K.P. (1991) Membrane organization of the dystrophin–glycoprotein complex. Cell, 66, 1121–1131.[Web of Science][Medline]
36 Ervasti, J.M., Ohlendieck, K., Kahl, S.D., Gaver, M.G. and Campbell, K.P. (1990) Deficiency of a glycoprotein component of the dystrophin complex in dystrophic muscle. Nature, 345, 315–319.[Medline]
37
Sicinski, P., Geng, Y., Ryder-Cook, A.S., Barnard, E.A., Darlison, M.G. and Barnard, P.J. (1989) The molecular basis of muscular dystrophy in the mdx mouse: a point mutation. Science, 244, 1578–1580.
38 Kimes, B.W. and Brandt, B.L. (1976) Characterization of two putative smooth muscle cell lines from rat thoracic aorta. Exp. Cell Res., 98, 349–366.[Web of Science][Medline]
39 Ibraghimov-Beskrovnaya, O., Ervasti, J.M., Leveille, C.J., Slaughter, C.A., Sernett, S.W. and Campbell, K.P. (1992) Primary structure of dystrophin-associated glycoproteins linking dystrophin to the extracellular matrix. Nature, 355, 696–702.[Medline]
40 Henry, M.D. and Campbell, K.P. (1998) A role for dystroglycan in basement membrane assembly. Cell, 95, 859–870.[Web of Science][Medline]
41
Thompson, T.G., Chan, Y.M., Hack, A.A., Brosius, M., Rajala, M., Lidov, H.G., McNally, E.M., Watkins, S. and Kunkel, L.M. (2000) Filamin 2 (FLN2): a muscle-specific sarcoglycan interacting protein. J. Cell Biol., 148, 115–126.
42 Zhu, X., Hadhazy, M., Wehling, M., Tidball, J.G. and McNally, E.M. (2000) Dominant negative myostatin produces hypertrophy without hyperplasia in muscle. FEBS Lett., 474, 71–75.[Web of Science][Medline]
43 Nagahara, H., Vocero-Akbani, A.M., Snyder, E.L., Ho, A., Latham, D.G., Lissy, N.A., Becker-Hapak, M., Ezhevsky, S.A. and Dowdy, S.F. (1998) Transduction of full-length TAT fusion proteins into mammalian cells: TAT-p27Kip1 induces cell migration. Nat. Med., 4, 1449–1452.[Web of Science][Medline]
44
Bonnemann, C.G., Passos-Bueno, M.R., McNally, E.M., Vainzof, M., de Sa Moreira, E., Marie, S.K., Pavanello, R.C., Noguchi, S., Ozawa, E., Zatz, M. et al. (1996) Genomic screening for beta-sarcoglycan gene mutations: missense mutations may cause severe limb-girdle muscular dystrophy type 2E (LGMD 2E). Hum. Mol. Genet., 5, 1953–1961.
45
Yoshida, T., Pan, Y., Hanada, H., Iwata, Y. and Shigekawa, M. (1998) Bidirectional signaling between sarcoglycans and the integrin adhesion system in cultured L6 myocytes. J. Biol. Chem., 273, 1583–1590.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  G. Anastasi, G. Cutroneo, A. Sidoti, C. Rinaldi, D. Bruschetta, G. Rizzo, R. D'Angelo, G. Tarone, A. Amato, and A. Favaloro Sarcoglycan Subcomplex Expression in Normal Human Smooth Muscle J. Histochem. Cytochem., August 1, 2007; 55(8): 831 - 843. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. T. Esapa, A. Waite, M. Locke, M. A. Benson, M. Kraus, R.A. J. McIlhinney, R. V. Sillitoe, P. W. Beesley, and D. J. Blake SGCE missense mutations that cause myoclonus-dystonia syndrome impair {varepsilon}-sarcoglycan trafficking to the plasma membrane: modulation by ubiquitination and torsinA Hum. Mol. Genet., February 1, 2007; 16(3): 327 - 342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T. Wheeler, C. E. Korcarz, K. A. Collins, K. A. Lapidos, A. A. Hack, M. R. Lyons, S. Zarnegar, J. U. Earley, R. M. Lang, and E. M. McNally Secondary Coronary Artery Vasospasm Promotes Cardiomyopathy Progression Am. J. Pathol., March 1, 2004; 164(3): 1063 - 1071. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.T. WHEELER, M.J. ALLIKIAN, A. HEYDEMANN, and E.M. MCNALLY The Sarcoglycan Complex in Striated and Vascular Smooth Muscle Cold Spring Harb Symp Quant Biol, January 1, 2002; 67(0): 389 - 398. [Abstract] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||