Merosin (laminin-2) localization in basal lamina of normal skeletal muscle fibers and changes in plasma membrane of merosin-deficient skeletal muscle fibers.
Primary deficiency of merosin causes a severe congenital muscular dystrophy (CMD) and a mouse dystrophy (dy/dy mouse). Also, its secondary deficiency is seen in some CMD with abnormal glycosylation of Alpha-dystroglycan, an extracellular membrane protein, which is the receptor of merosin and binds to dystrophin underlying the sarcolenma via Beta-dystroglycan, a transmembrane protein. In immunogold and freeze-etch electron microscopic studies, merosin in basal lamina of normal skeletal muscles has a zonation in the distribution and is localized at the lamina lucida of muscle basal lamina, and dystrophin molecules are often closed to merosin molecules at the inside and outside surface of muscle plasma membrane. Moreover, merosin molecules exist as the short fine cross-bridge fibrils connecting the basal lamina to the neighboring outer leaflet of the muscle plasma membrane. In freeze-fracture studies, the changes in muscle plasma membranes of dy/dy mice reveal a markedly decreased density of orthogonal arrays (OAs) but normal density of intramembranous particles (IMPs), whereas depletions of IMPs with decreased OAs have been found in Fukyama-type congenital muscular dystrophy, Duchenne muscular dystrophy, and mdx mice. Thus, further studies including the functional role of OAs would be required to understand the pathomechanism of merosin-deficient CMD.
Shibuya
Seiji
S
Department of Neurology, Showa University Fujigaoka Hospital, Aoba-Ku, Yokohama 227-8517, Japan. seiji-shibuya@nifty.com
Wakayama
Yoshihiro
Y
Inoue
Masahiko
M
Kojima
Hiroko
H
Oniki
Hiroaki
H
D000818:Animals; D001485:Basement Membrane / Q000648:ultrastructure; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D007797:Laminin / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D008818:Mice, Neurologic Mutants; D008854:Microscopy, Electron; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000648:ultrastructure*; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000378:metabolism*
D007797:Laminin; C102645:laminin alpha 2