Imamura M, Araishi K, Noguchi S, Ozawa E
Department of Cell Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8502, Japan.
Hum Mol Genet. 2000 Dec 12;9(20):3091-100. doi: 10.1093/hmg/9.20.3091.
The dystrophin-associated membrane-integrated protein complex anchors dystrophin in the sarcolemma of striated muscles and is composed of two glycoprotein subcomplexes, the dystroglycan and the sarcoglycan (SG) complexes, and a small membrane protein termed sarcospan (SPN). The SG complex consists of four transmembrane glycoproteins, alpha-SG, beta-SG, gamma-SG and delta-SG. We found that beta-SG and delta-SG were co-expressed with epsilon-SG, a alpha-SG homolog, in the peripheral nerve, but not with alpha-SG or gamma-SG. SPN, which tightly links to the SG complex in the muscle cell membrane, was absent in the peripheral nerve. These peripheral nerve SGs were colocalized at the outermost layer of the myelin sheath of nerve fibers together with the dystroglycan complex, utrophin, and a short dystrophin isoform (Dp116). Immunocytochemical analysis using SG-deficient animals showed that a defect in beta- or delta-SG led to a great reduction of all residual SGs, but not of the other proteins, i.e., dystroglycans, Dp116 and utrophin, in the peripheral nerve. This observation suggests that the epsilon-, beta- and delta-SG molecules form a complex behaving as a single unit similar to the SG complex in muscle cells. An immunoprecipitation study indicated that the SG complex is associated with the dystroglycan complex and Dp116 or utrophin. These results demonstrated that Dp116 and utrophin are anchored to a novel membrane protein architecture, which consists of the SG and dystroglycan complexes, but not SPN, in the Schwann cell membrane.
肌营养不良蛋白相关的膜整合蛋白复合物将肌营养不良蛋白锚定在横纹肌的肌膜中，由两个糖蛋白亚复合物、肌营养不良聚糖和肌聚糖（SG）复合物以及一种称为肌膜跨度蛋白（SPN）的小膜蛋白组成。SG复合物由四种跨膜糖蛋白组成，即α-SG、β-SG、γ-SG和δ-SG。我们发现，β-SG和δ-SG与α-SG的同源物ε-SG在外周神经中共表达，但不与α-SG或γ-SG共表达。在肌细胞膜中与SG复合物紧密相连的SPN在外周神经中不存在。这些外周神经SG与肌营养不良聚糖复合物、抗肌萎缩蛋白和一种短的肌营养不良蛋白异构体（Dp116）一起共定位于神经纤维髓鞘的最外层。使用SG缺陷动物的免疫细胞化学分析表明，β-或δ-SG的缺陷导致外周神经中所有残留SG的大量减少，但不会导致其他蛋白质（即肌营养不良聚糖、Dp116和抗肌萎缩蛋白）的减少。这一观察结果表明，ε-、β-和δ-SG分子形成一个复合物，其行为类似于肌肉细胞中的SG复合物。免疫沉淀研究表明，SG复合物与肌营养不良聚糖复合物以及Dp116或抗肌萎缩蛋白相关。这些结果表明，Dp116和抗肌萎缩蛋白锚定在施万细胞膜中的一种新型膜蛋白结构上，该结构由SG和肌营养不良聚糖复合物组成，但不包括SPN。
