Disease relevance of SGCB

• Beta-sarcoglycan (A3b) mutations cause autosomal recessive muscular dystrophy with loss of the sarcoglycan complex [1].
• Beta-sarcoglycan: characterization and role in limb-girdle muscular dystrophy linked to 4q12 [2].
• Limb-girdle muscular dystrophy type 2E (LGMD 2E) is caused by mutations in the beta-sarcoglycan gene, which is expressed in skeletal, cardiac, and smooth muscle. beta-sarcoglycan-deficient (Sgcb-null) mice developed severe muscular dystrophy and cardiomyopathy with focal areas of necrosis [3].
• Neoglycoconjugates derived from GlcC, GalC (type I and II and the behenic analog), SGC, LC, and Gb3C were recognized by the recombinant human immunodeficiency virus coat protein gp120 (rgp120) [4].
• Immunofluorescence and immunogold labelling were used to localise the 43-kDa dystrophin-associated glycoprotein (43DAG) of the dystrophin-glycoprotein complex in control and Duchenne muscular dystrophy (DMD) biopsies [5].

High impact information on SGCB

• Screening for sarcoglycan-gene mutations in 50 of the 54 patients revealed mutations in 29 patients (58 percent): 17 (34 percent) had mutations in the alpha-sarcoglycan gene, 8 (16 percent) in the beta-sarcoglycan gene, and 4 (8 percent) in the gamma-sarcoglycan gene [6].
• Immunostaining of her muscle biopsy shows specific loss of the components of the sarcoglycan complex (beta-sarcoglycan, alpha-sarcoglycan (adhalin), and 35 kD sarcoglycan) [1].
• We have cloned human beta-sarcoglycan cDNA and mapped the beta-sarcoglycan gene to chromosome 4q12 [2].
• Immunohistochemical and immunoblot analyses of BSG(-)(/-)mice demonstrated that deficiency of beta-sarcoglycan also caused loss of all of the other sarcoglycans as well as of sarcospan in the sarcolemma [7].
• Genomic screening for beta-sarcoglycan gene mutations: missense mutations may cause severe limb-girdle muscular dystrophy type 2E (LGMD 2E) [8].

Biological context of SGCB

• The open reading frame of the beta-sarcoglycan coding region extends over six exons [8].
• Overexpression of gamma-sarcoglycan lead to the up-regulation of alpha- and beta-sarcoglycan [9].
• All seven beta-sarcoglycan mutations reported to date are associated with a severe phenotype and occur in exons 3 and 4, which correspond to the immediate extracellular domain of the protein [10].
• We found that the 8 bp duplication in the beta-sarcoglycan gene and the 1 bp insertion in the gamma-sarcoglycan gene are in linkage disequilibrium with neighbouring polymorphisms [11].
• delta-Sarcoglycan (delta-SG) is one of the first proteins of the sarcoglycan complex (SGC) to be expressed during muscle development, and it has been considered fundamental for the assembling and insertion of the SGC in the sarcolemma [12].

Anatomical context of SGCB

• Immunohistochemical analysis of skeletal muscle biopsies from patients with LGMD2C, LGMD2D, and LGMD2E demonstrated a reduction of the entire sarcoglycan complex in these muscular dystrophies [13].
• The sarcoglycan subcomplex (SGC) is a well-known system of interaction between extracellular matrix and sarcolemma-associated cytoskeleton in skeletal and cardiac muscle [14].
• When beta-sarcoglycan was expressed appropriately at the sarcolemma of gamma-sarcoglycan-deficient patients, intracellular labeling of beta-sarcoglycan was also present [15].
• Defective assembly of sarcoglycan complex in patients with beta-sarcoglycan gene mutations. Study of aneural and innervated cultured myotubes [16].
• Dystrophin-associated protein, 43DAG, was detected in all the tissues examined, but 50DAG was detected only in skeletal and cardiac muscles [17].

Associations of SGCB with chemical compounds

• The patient's sample showed a band of increased mobility in exon 4 of the beta-sarcoglycan gene which, upon sequencing, was found to represent a homozygous A-->G transversion at nucleotide 551, resulting in a tyrosine to cysteine substitution at position 184 (Y184C) [10].
• Multiple ligand co-recognition of 3'-sulfogalactosylceramide (SGC) and sulfotyrosine initiated the comparison of SGC and sulfotyrosine and, subsequently, phosphotyrosine (pY) binding [18].
• A variety of natural glycosphingolipids (GSLs): GlcC, GalC, SGC, LC, Gb3C, Gb4C, Gg4C, Gb5C, and GM1C, gave the corresponding acids: 2-hydroxy-3-(N-acyl)-4-(O-glycosyl)-oxybutyric acids, i.e. "glycosyl ceramide acids" (GSL.CCOOH) in excellent yields (80-90%) [4].
• Using hsp70, anti-SGC, and anti-pY antibodies, ligand binding is retained following phosphate/sulfate and tyrosine/galactose substitution in SGC and sulfate/phosphate exchange in pY [18].
• In addition, in teased nerve preparations, mAb 224-58-positive cells were also galactosylceramide (GalC)- and SGC-positive [19].

Physical interactions of SGCB

• (a) Among the components of the glycoprotein complex which links dystrophin to the sarcolemma, a 43-kDa dystrophin-associated glycoprotein binds directly to dystrophin [20].

Other interactions of SGCB

• The genes for LGMD2C, LGMD2D and LGMD2E code for proteins of the SG complex [21].
• In the present study, through screening 80 unrelated LGMD2 families, we identified 13 families with LGMD2E [22].
• A3b is a novel dystrophin-associated glycoprotein with an approximate molecular mass of 43 kd but is distinct from 43DAG [23].
• Pathogenetic mutations involving one gene for sarcoglycan complex components were identified in 13 patients: alpha-sarcoglycan in seven, beta-sarcoglycan in two, gamma-sarcoglycan in four, and none in the delta-sarcoglycan gene [24].
• Beta-sarcoglycan-deficient patients showed poor localization of extracellular matrix proteins in addition to a complete absence of the sarcoglycans [15].

Analytical, diagnostic and therapeutic context of SGCB

• In the present study, we examined the striated muscles of the dystrophic hamster with anti-A3b antibody in addition to anti-50DAG, anti-43DAG, anti-35DAG, anti-dystrophin, and anti-laminin antibodies by both immunohistochemistry and immunoblot analysis and found that 50DAG, A3b, and 35DAG are selectively lost [23].
• We show by immunofluorescence and Western blotting that in skeletal muscle from these patients gamma-sarcoglycan is completely absent and alpha- and beta-sarcoglycan are greatly reduced in abundance, whereas other components of the DGC are preserved [25].
• Advanced light-microscopic imaging techniques demonstrated that co-expression of beta-sarcoglycan and delta-sarcoglycan is also responsible for delivery to and retention of sarcoglycan subcomplexes at the cell surface [26].
• We have analyzed the distribution of the five tetrameric Bandeiraea simplicifolia I isolectins (A4, A3b, A2B2, AB3, B4) isolated by melibionate Bio-Gel affinity chromatography from 168 single seeds gathered in Ghana from known trees and pods [27].
• This suggests that although 224-58 does not discriminate between SGC and seminolipid in serological tests, these lipids in their naturally occurring membrane acquire a spatial configuration that renders them distinguishable to their respective antibody [19].

References