Abstract
The sarcoglycan complex is known to be involved in limb-girdle muscular dystrophy (LGMD) and is composed of at least three proteins: alpha-, beta-, and gamma-sarcoglycan. delta-Sarcoglycan has now been identified as a second 35-kDa sarcolemmal transmembrane glycoprotein that shares high homology with gamma-sarcoglycan and is expressed mainly in skeletal and cardiac muscle. Biochemical analysis has demonstrated that gamma- and delta-sarcoglycan are separate entities within the sarcoglycan complex and that all four sarcoglycans exist in the complex on a stoichiometrically equal basis. 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. Furthermore, we have mapped the human delta-sarcoglycan gene to chromosome 5q33-q34 in a region overlapping the recently linked autosomal recessive LGMD2F locus.
Highlights
The sarcoglycan complex is known to be involved in limb-girdle muscular dystrophy (LGMD) and is composed of at least three proteins: ␣, , and ␥-sarcoglycan. ␦-Sarcoglycan has been identified as a second 35kDa sarcolemmal transmembrane glycoprotein that shares high homology with ␥-sarcoglycan and is expressed mainly in skeletal and cardiac muscle
The dystrophin-glycoprotein complex (DGC)1 [1,2,3,4] in skeletal muscle is a complex of sarcolemmal proteins and glycoproteins. It is composed of dystrophin, a cytoskeletal actin-binding protein [5,6,7]; the syntrophins, a 59-kDa triplet of intracellular proteins that bind the C-terminal domain of dystrophin (8 –12); ␣-dystroglycan, a 156-kDa extracellular proteoglycan that binds the G domain of laminin [13,14,15]; -dystroglycan, a 43kDa transmembrane glycoprotein [2, 3, 13] that binds the cysteine-rich region of dystrophin [16, 17]; ␣, , and ␥-sarcogly
We demonstrate that ␦-sarcoglycan is reduced along with ␣, , and ␥-sarcoglycan in LGMD2C, -2D, and -2E
Summary
Peptide Sequencing and Isolation of Human ␦-Sarcoglycan cDNA—Peptides of the 35-kDa component of purified rabbit skeletal muscle DGC were obtained as described previously [24]. These peptide sequences were used to search the data base of expressed sequence tags (dbEST) using the TBLASTN search program at the National Center for Biotechnology Information. Immunoblot and Immunofluorescence Analysis—Crude rabbit skeletal muscle sarcolemma, purified DGC [46, 47], and isolated sarcoglycan complex [47] were prepared as described previously. The purified tryptic peptides were sequenced by Automated Edman degradation using an Applied Biosystems model 470A sequencer equipped with an on-line model 120A phenylthiohydantoin derivative analyzer using the manufacturer’s standard programming and chemicals
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