Grady R M, Merlie J P, Sanes J R
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Cell Biol. 1997 Feb 24;136(4):871-82. doi: 10.1083/jcb.136.4.871.
Utrophin is a large cytoskeletal protein that is homologous to dystrophin, the protein mutated in Duchenne and Becker muscular dystrophy. In skeletal muscle, dystrophin is broadly distributed along the sarcolemma whereas utrophin is concentrated at the neuromuscular junction. This differential localization, along with studies on cultured cells, led to the suggestion that utrophin is required for synaptic differentiation. In addition, utrophin is present in numerous nonmuscle cells, suggesting that it may have a more generalized role in the maintenance of cellular integrity. To test these hypotheses we generated and characterized utrophin-deficient mutant mice. These mutant mice were normal in appearance and behavior and showed no obvious defects in muscle or nonmuscle tissue. Detailed analysis, however, revealed that the density of acetylcholine receptors and the number of junctional folds were reduced at the neuromuscular junctions in utrophin-deficient skeletal muscle. Despite these subtle derangements, the overall structure of the mutant synapse was qualitatively normal, and the specialized characteristics of the dystrophin-associated protein complex were preserved at the mutant neuromuscular junction. These results point to a predominant role for other molecules in the differentiation and maintenance of the postsynaptic membrane.
肌养蛋白是一种大型细胞骨架蛋白，与杜兴氏和贝克氏肌营养不良症中发生突变的肌营养不良蛋白同源。在骨骼肌中，肌营养不良蛋白广泛分布于肌膜，而肌养蛋白则集中在神经肌肉接头处。这种差异定位以及对培养细胞的研究表明，肌养蛋白是突触分化所必需的。此外，肌养蛋白存在于许多非肌肉细胞中，这表明它可能在维持细胞完整性方面具有更广泛的作用。为了验证这些假设，我们培育并鉴定了肌养蛋白缺陷型突变小鼠。这些突变小鼠外观和行为正常，在肌肉或非肌肉组织中未表现出明显缺陷。然而，详细分析表明，肌养蛋白缺陷型骨骼肌的神经肌肉接头处乙酰胆碱受体密度和突触褶皱数量减少。尽管存在这些细微紊乱，但突变突触的整体结构在质量上是正常的，并且肌营养不良蛋白相关蛋白复合物的特殊特征在突变神经肌肉接头处得以保留。这些结果表明其他分子在突触后膜的分化和维持中起主要作用。
