Immunogold EM reveals a close association of plectin and the desmin cytoskeleton in human skeletal muscle

Plectin is a multifunctional cytoskeletal linker protein with an intermedia te filament-binding site and sequence elements with high homology to actin- binding domains. Mutations of the human plectin gene as well as the targete d inactivation of its murine analog cause a generalized blistering skin dis order and muscular dystrophy, thus implying its essential role in cells tha t are exposed to mechanical stress. In the present study we report the characterization of two nov domain-speci fic plectin antibodies as well as ultrastructural localization of plectin i n normal human skeletal muscle. Using immunogold electron microscopy, we lo calized plectin at three prominent sites: 1) Plectin is found at regularly spared intervals along the cytoplasmic face of the plasma membrane. 2) It i s distinctly localized at filamaentous bridges between Z-lines of periphera l myofibrils and the sarcolemma and 3) at structures forming the intermyofi brillar scaffold, At the latter two locations, plectin and desmin were foun d to colocalize. Our ultrastructural analysis suggests that plectin may hav e a central role in the structural and functional organization of the inter mediate filament cytoskeleton in mature human skeletal muscle.