Saito F, Masaki T, Kamakura K, Anderson L V, Fujita S, Fukuta-Ohi H, Sunada Y, Shimizu T, Matsumura K
Department of Neurology and Neuroscience, Teikyo University School of Medicine, Tokyo 173-8605, Japan.
J Biol Chem. 1999 Mar 19;274(12):8240-6. doi: 10.1074/jbc.274.12.8240.
We have demonstrated previously 1) that the dystroglycan complex, but not the sarcoglycan complex, is expressed in peripheral nerve, and 2) that alpha-dystroglycan is an extracellular laminin-2-binding protein anchored to beta-dystroglycan in the Schwann cell membrane. In the present study, we investigated the transmembrane molecular architecture of the dystroglycan complex in Schwann cells. The cytoplasmic domain of beta-dystroglycan was co-localized with Dp116, the Schwann cell-specific isoform of dystrophin, in the abaxonal Schwann cell cytoplasm adjacent to the outer membrane. beta-dystroglycan bound to Dp116 mainly via the 15 C-terminal amino acids of its cytoplasmic domain, but these amino acids were not solely responsible for the interaction of these two proteins. Interestingly, the beta-dystroglycan-precipitating antibody precipitated only a small fraction of alpha-dystroglycan and did not precipitate laminin and Dp116 from the peripheral nerve extracts. Our results indicate 1) that Dp116 is a component of the submembranous cytoskeletal system that anchors the dystroglycan complex in Schwann cells, and 2) that the dystroglycan complex in Schwann cells is fragile compared with that in striated muscle cells. We propose that this fragility may be attributable to the absence of the sarcoglycan complex in Schwann cells.
1）在周围神经中表达的是肌营养不良聚糖复合物，而非肌聚糖复合物；2）α-肌营养不良聚糖是一种细胞外层粘连蛋白-2结合蛋白，锚定在施万细胞膜中的β-肌营养不良聚糖上。在本研究中，我们研究了施万细胞中肌营养不良聚糖复合物的跨膜分子结构。β-肌营养不良聚糖的胞质结构域与肌营养不良蛋白的施万细胞特异性同工型Dp116，在靠近外膜的轴突外施万细胞胞质中共定位。β-肌营养不良聚糖主要通过其胞质结构域的15个C末端氨基酸与Dp116结合，但这些氨基酸并非这两种蛋白质相互作用的唯一原因。有趣的是，β-肌营养不良聚糖沉淀抗体仅沉淀了一小部分α-肌营养不良聚糖，且未从周围神经提取物中沉淀出层粘连蛋白和Dp116。我们的结果表明：1）Dp116是将肌营养不良聚糖复合物锚定在施万细胞中的膜下细胞骨架系统的一个组成部分；2）与横纹肌细胞相比，施万细胞中的肌营养不良聚糖复合物较为脆弱。我们认为这种脆弱性可能归因于施万细胞中不存在肌聚糖复合物。
