Abstract
The dystroglycan (DG) expression pattern can be altered in severe muscular dystrophies. In fact, some congenital muscular dystrophies (CMDs) and limb-girdle muscular dystrophies (LGMDs) are caused by point mutations identified in six glycosyltransferase genes which are likely to target different steps along the posttranslational “O-glycosylation route” leading to a fully decorated and functional α-DG subunit. Indeed, hypoglycosylation of α-DG is thought to represent a major pathological event, in that it could reduce the DG’s ability to bind the basement membrane components, thus leading to sarcolemmal instability and necrosis. In order to set up an efficient standard immunological protocol, taking advantage of a wide panel of antibodies, we have analyzed the two DG subunits in a small cohort of adult dystrophic patients, whom an extensive medical examination had already clinically classified as affected by LGMD (5), Miyoshi (1) or distal (1) myopathy. Immunofluorescence analysis of skeletal muscle tissue sections revealed a proper sarcolemmal localization of the DG subunits in all the patients analyzed. However, Western blot analysis of lectin enriched skeletal muscle samples revealed an abnormal glycosylation of α-DG in two patients. Our work reinforces the notion that a careful immunological and biochemical analysis of the two DG subunits should be always considered as a prerequisite for the identification of new putative cases of dystroglycanopathy.
Highlights
The dystrophin-glycoprotein complex (DGC) represents a group of cytoskeletal, transmembrane and peripheral proteins linking the extracellular matrix to the actincytoskeleton in a wide variety of human tissues, ranging from muscle to central and peripheral nervous system, as well as the airways, lung or kidney epithelia [1]
At least 8 genes have been linked to these disorders, namely the glycosyltransferases Protein-O-mannosyl transferase 1 (POMT1), Protein-O-mannosyl transferase 2 (POMT2) and Protein-O-mannose 1,2-N-acetylglucosaminyltransferase 1 (POMGnT1), three enzymes whose functions remain uncharacterized, Fukutin, Fukutin-related protein (FKRP) and LARGE, and two subunits (DPM1 and DPM2) of dolicholphosphate-mannose (Dol-P-Man) synthase [9, 10]
In this study we analyzed the DG subunits, - and -DG, in a small cohort of seven patients that have all been classified as affected by non-congenital muscular dystrophies by clinical examination, in order to assess the possible involvement of DG in limb-girdle muscular dystrophies (LGMDs) and distal myopathy phenotypes
Summary
The dystrophin-glycoprotein complex (DGC) represents a group of cytoskeletal, transmembrane and peripheral proteins linking the extracellular matrix to the actincytoskeleton in a wide variety of human tissues, ranging from muscle (skeletal,cardiac or smooth) to central and peripheral nervous system, as well as the airways, lung or kidney epithelia [1]. In this study we analyzed the DG subunits, - and -DG, in a small cohort of seven patients that have all been classified as affected by non-congenital muscular dystrophies by clinical examination, in order to assess the possible involvement of DG in LGMDs and distal myopathy phenotypes.
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