Matsumura K, Tomé F M, Collin H, Leturcq F, Jeanpierre M, Kaplan J C, Fardeau M, Campbell K P
Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City 52242.
Neuromuscul Disord. 1994 Mar;4(2):115-20. doi: 10.1016/0960-8966(94)90002-7.
The dystrophin-glycoprotein complex spans the sarcolemma to provide a linkage between the subsarcolemmal cytoskeleton and the extracellular matrix in skeletal muscle. In Duchenne muscular dystrophy (DMD), the absence of dystrophin leads to a drastic reduction in all of the dystrophin-associated proteins in the sarcolemma, thus causing the disruption of the dystrophin-glycoprotein complex and the loss of the linkage to the extracellular matrix. This is presumed to lead to sarcolemmal instability which could render muscle fibers susceptible to necrosis. In DMD, a very small percentage of muscle fibers show dystrophin staining along the sarcolemma, presumably due to a second in-frame deletion in the dystrophin gene. However, the functional significance of these rare dystrophin-positive muscle fibers (revertants) in DMD has been unclear. Here we report the co-expression of the dystrophin-associated proteins with dystrophin in revertants of DMD skeletal muscle. Our results suggest that the entire dystrophin-glycoprotein complex is restored in revertants and, thus, the linkage between the subsarcolemmal cytoskeleton and the extracellular matrix is restored in these muscle fibers.
肌营养不良蛋白 - 糖蛋白复合物横跨肌膜，在骨骼肌的肌膜下细胞骨架与细胞外基质之间建立联系。在杜兴氏肌营养不良症（DMD）中，肌营养不良蛋白的缺失导致肌膜中所有与肌营养不良蛋白相关的蛋白质大幅减少，从而导致肌营养不良蛋白 - 糖蛋白复合物的破坏以及与细胞外基质联系的丧失。据推测，这会导致肌膜不稳定，使肌纤维易发生坏死。在DMD中，极少数肌纤维沿肌膜显示肌营养不良蛋白染色，推测这是由于肌营养不良蛋白基因中的第二个框内缺失所致。然而，这些罕见的肌营养不良蛋白阳性肌纤维（回复体）在DMD中的功能意义尚不清楚。在此，我们报告了DMD骨骼肌回复体中肌营养不良蛋白相关蛋白与肌营养不良蛋白的共表达。我们的结果表明，回复体中整个肌营养不良蛋白 - 糖蛋白复合物得以恢复，因此，这些肌纤维中肌膜下细胞骨架与细胞外基质之间的联系也得以恢复。
