Trans‐sarcolemmal proteins situated central to the subsarcolemmal region

Abstract

Trans‐sarcolemmal proteins located inside, within, and outside of the muscle fibre plasma membrane fall into two categories, the dystrophin‐glycoprotein complex (DGC) and non‐DGC‐related proteins, e.g. dysferlin, caveolin, dystrobrevins and syntrophins. Mutational defects are responsible for their immunohistochemical absence or reduction giving rise to certain muscular dystrophies. In other neuromuscular disorders, i.e. inflammatory, metabolic, and neurogenic processes, transarcolemmal proteins are well preserved. Unlike desmin and plectin, which form a honeycomb‐type network across the muscle fibre and a subsarcolemmal layer, trans‐sarcolemmal proteins are not expressed central to the subsarcolemmal region in normal mature muscle fibres. In three different types of lesion, transarcolemmal proteins may be encountered within muscle fibres unrelated to the subsarcolemmal region: (1) immature fibres: dysferlin and caveolin different from the absence of DGC proteins in regenerating muscle fibres and, thereby, underscoring their different transcellular trafficking; (2) lining autophagic vacuoles and pseudo‐vacuoles identified by invagination of the sarcolemma; (3) accruing within core‐like lesions marked by sarcomeric disintegration and in association with the accumulation of other proteins, e.g. desmin, α‐B crystallin. Our differential diagnostic studies indicate that different trans‐sarcolemmal proteins are encountered central to the subsarcolemmal region in different myopathological conditions and therefore for different pathogenetic reasons.Acknowledgements: These studies have been supported by the Deutsche Gesellschaft für Muskelkranke e.V., Freiburg/Germany, the European Neuromuscular Centre (ENM), Baarn/The Netherlands, and the ‘MAIFOR’ programme of the Johannes Gutenberg University, Mainz/Germany.