Dystrophin is required for normal thin filament-membrane associations at myotendinous junctions.
Dystrophin, the deficient gene product in Duchenne muscular dystrophy, is located subjacent to the muscle cell membrane at myotendinous junctions, as well as along the entire muscle cell. Myotendinous junctions are sites at which thin filaments normally are linked to one another and to the cell membrane, by both lateral and end-on associations between the thin filaments and membrane. The cell membrane at these sites in normal muscle is folded extensively. Dystrophic junctions display normal contacts between the ends of thin filaments and subsarcolemmal densities. However dystrophic junctions are deficient in lateral associations between thin filaments and the membrane and display less membrane folding than controls. These structural defects would result in stress concentrations at sites of thin filament attachment to the membrane, which can cause membrane tearing during muscle activation, especially in large-diameter and mature muscle cells. This deficiency in dystrophic myotendinous junction structure may contribute to our understanding of previously unaccountable aspects of the etiology of Duchenne muscular dystrophy.
Tidball
J G
JG
Department of Kinesiology, University of California, Los Angeles 90024.
Law
D J
DJ
D000818:Animals; D016189:Dystrophin / Q000172:deficiency*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D009132:Muscles / Q000648:ultrastructure*; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D012016:Reference Values; D013710:Tendons / Q000648:ultrastructure*
D016189:Dystrophin