Altered distribution of plectin/HD1 in dystrophinopathies.
Plectin/HD1 is a high molecular weight protein (approximately 500 kDa) that has been proposed to act as an important and versatile cytoskeletal cross-linker molecule. Mutations of the human plectin gene have recently been associated with the autosomal recessive disorder epidermolysis bullosa simplex with muscular dystrophy. We studied the expression of plectin/HD1 in various neuromuscular disorders by indirect immunofluorescence. 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 fiber type-related expression was significantly altered in the group of dystrophinopathies, whereas it was maintained in all other myopathies and denervating disorders. In seven dystrophinopathies studied, a markedly increased plectin/HD1 immunoreactivity at the sarcolemmal level of type 2 fibers was observed. Confocal laser microscopy of normal skeletal muscle revealed a colocalization of desmin and plectin/HD1 at the level of the sarcolemma. This suggests that plectin/HD1- in analogy to its demonstrated involvement in cytokeratin-hemidesmosome linkage in epidermis-may mediate the anchorage of desmin to the sarcolemma (i.e. to costameres).
Schröder
R
R
Neurologische Klinik und Poliklinik, Universität Bonn, Germany.
Mundegar
R R
RR
Treusch
M
M
Schlegel
U
U
Blümcke
I
I
Owaribe
K
K
Magin
T M
TM
D015139:Blotting, Southern; D015153:Blotting, Western; D005796:Genes; D006801:Humans; D007381:Intermediate Filament Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D018482:Muscle, Skeletal / Q000737:chemistry / Q000648:ultrastructure; D009136:Muscular Dystrophies / Q000378:metabolism; D009468:Neuromuscular Diseases / Q000378:metabolism*; D051190:Plectin
D007381:Intermediate Filament Proteins; C495332:PLEC protein, human; D051190:Plectin