ALTERED DISTRIBUTION OF PLECTIN HD1 IN DYSTROPHINOPATHIES/

Plectin/HD1 is a high molecular weight protein (similar to 500 kDa) th at has been proposed to act as an important and versatile cytoskeletal crosslinker molecule. Mutations of the human plectin gene have recent ly been associated with the autosomal recessive disorder epidermolysis bullosa simplex,vith muscular dystrophy. We studied the expression of plectin/HD1 in various neuromuscular disorders by indirect immunofluo rescence. In cross sections of normal human muscle, plectin/HD1 showed a checkerboard-like distribution with moderate to intense cytoplasmic and sarcolemmal staining in type 1 fibers and a faint staining of the sarcolemma in type 2 fibers. In longitudinal sections of plectin/HD1- positive fibers a cross-striation staining pattern was noted, This fib er type-related expression was significantly altered in the group of d ystrophinopathies, whereas it was maintained in all other myopathies a nd denervating disorders, In seven dystrophinopathies studied, a marke dly increased plectin/HD1 immunoreactivity at the sarcolemmal level of type 2 fibers was observed, Confocal laser microscopy of normal skele tal muscle revealed a colocalization of desmin and plectin/HD1 at the level of the sarcolemma. This suggests that plectin/HD1 - in analogy t o its demonstrated involvement in cytokeratin-hemidesmosome linkage in epidermis-may mediate the anchorage of desmin to the sarcolemma (i.e. to costameres).