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MOLECULAR MECHANISM OF PERIPHEARAL MYELINOGENESIS

外周髓鞘生成的分子机制

基本信息

批准号：
10044319
负责人：
MATSUMURA Kiichiro
金额：
$ 7.55万
依托单位：
Teikyo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

In Schwann cells, the transmembrane glycoproteinβ-dystroglycan composes the dystroglycan complex, together with the extracellular glycoprotein α-dystroglycan which binds laminin-2, a major component of the Schwann cell basal lamina. In order to provide clues to the biological functions of the interaction of the dystroglycan complex with laminin-2 in peripheral nerve, the expression of β-dystroglycan and laminin-α2 chain was studied in rat sciatic nerves undergoing axonal degeneration and regeneration as well as in normal condition. In normal sciatic nerve, immunoreactivity for the cytoplasmic domain of β-dystroglycan was consistently and selectively localized in the Schwann cell cytoplasm underlying the outer (abaxonal) membrane apposing the basal lamina. While β-dystroglycan expression was gradually downregulated in Schwann cells losing contact with axons during axonal degeneration, it was progressively upregulated as the regenerating process of ensheathment and myelination proceeded during regeneration. Interestingly, β-dystroglycan expression, when detectable, was always restricted to the Schwann cell cytoplasm beneath the outer membrane apposing the basal lamina during both axonal degeneration and regeneration. Furthermore, laminin-α2 immunoreactivity roughly paralleled that of β-dystroglycan during both axonal degeneration and regeneration, indicating that the expression of β-dystroglycan and laminin-α2 is induced and maintained by the Schwann cell contact with axons. Our results indicate that the dystroglycan complex is involved in the adhesion of the Schwann cell outer membrane with the basal lamina and suggest that the dystroglycan complex may play a role in the process of Schwann cell ensheathment and myelination through the interaction with laminin-2.

在许旺细胞中，跨膜糖蛋白β-肌营养不良聚糖与细胞外糖蛋白α-肌营养不良聚糖一起组成肌营养不良聚糖复合物，后者结合层粘连蛋白-2，是许旺细胞基底层的主要组分。为了探讨周围神经中肌营养不良蛋白聚糖复合物与层粘连蛋白2相互作用的生物学功能，本实验研究了β-肌营养不良蛋白聚糖和层粘连蛋白α2链在大鼠坐骨神经轴突变性、再生过程中的表达。在正常坐骨神经中，β-肌营养不良蛋白聚糖的胞质结构域的免疫反应性一致地且选择性地定位于与基底膜相对的外（轴突）膜下面的雪旺细胞胞质中。虽然在轴突变性期间失去与轴突接触的雪旺细胞中β-肌营养不良蛋白聚糖表达逐渐下调，但随着再生过程中鞘化和髓鞘形成的进行，β-肌营养不良蛋白聚糖表达逐渐上调。有趣的是，β-肌营养不良蛋白聚糖的表达，当可检测时，总是局限于外膜下的雪旺细胞胞质，并在轴突变性和再生过程中的基底层。此外，在轴突变性和再生期间，层粘连蛋白-α2的免疫反应性大致与β-肌营养不良蛋白聚糖的免疫反应性相同，表明β-肌营养不良蛋白聚糖和层粘连蛋白-α2的表达是由雪旺细胞与轴突接触诱导和维持的。我们的研究结果表明，肌营养不良蛋白聚糖复合物参与了雪旺细胞外膜与基底层的粘附，并表明肌营养不良蛋白聚糖复合物可能通过与层粘连蛋白-2的相互作用在雪旺细胞鞘化和髓鞘形成过程中发挥作用。