Abstract
Aberrant expression of the dystrophin-associated protein complex is thought to underlie the pathogenesis of Duchenne dystrophy, Becker muscular dystrophy, and severe childhood autosomal recessive muscular dystrophy. Recently, our laboratory identified an agrin receptor from Torpedo electric organ postsynaptic membranes. It is a heteromer of 190- and 50-kDa subunits with similarity to two components of the dystrophin-associated protein complex of alpha- and beta-dystroglycan. We now confirm the relationship between the Torpedo agrin receptor and mammalian dystroglycans and provide further information about the structure of the alpha-dystroglycan-beta-dystroglycan complex. The sequences of three peptides from each Torpedo subunit were 69% identical to mammalian dystroglycans. An antiserum to mammalian beta-dystroglycan recognizes the Torpedo 50-kDa polypeptide. Additionally, like alpha-dystroglycan, the 190-kDa agrin receptor subunit binds laminin. Previous studies have indicated that alpha- and beta-dystroglycan arise by cleavage of a precursor protein. Tryptic peptide mapping of both subunits and amino-terminal sequencing of Torpedo beta-dystroglycan indicate a single cleavage site, corresponding to serine 654 of the mammalian dystroglycan precursor. Gel electrophoresis analysis indicates there is at least one intrachain disulfide bond in beta-dystroglycan. These results provide precise primary structures for alpha- and beta-dystroglycan.
Highlights
Aberrant expression of the dystrophin-associated protein complex is thought to underlie the pathogenesis of Duchenne dystrophy, Becker muscular dystrophy, and severe childhood autosomal recessive muscular dystrophy
In this study we extend our examination of the relationship between Torpedo agrin receptor subunits and mammalian dystroglycans to three levels: peptide sequence, ligand binding, and antigenicity
Mammalian dystroglycan isolated from muscle plasma membranes is a detergent-soluble heteromer comprised of ␣- and -subunits [30]
Summary
Our laboratory identified an agrin receptor from Torpedo electric organ postsynaptic membranes It is a heteromer of 190- and 50-kDa subunits with similarity to two components of the dystrophinassociated protein complex of ␣- and -dystroglycan. Our search for the agrin receptor in postsynaptic membranes of Torpedo electroplax led to the discovery of a heteromeric complex of two membrane glycoproteins that based on amino acid sequence of two internal peptides share structural similarity with the dystroglycans [16]. Membrane Organization of the ␣-Dystroglycan--Dystroglycan Complex we have localized the cleavage site of the dystroglycan precursor in Torpedo, and present evidence suggesting that a similar site is used in mammalian dystroglycan These results provide an unambiguous primary structure for ␣- and -dystroglycan
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