MOLECULAR MECHANISM OF PERIPHEARAL MYELINOGENESIS

在雪旺细胞中，跨膜糖蛋白β-dystroglan与细胞外糖蛋白α-dystroglan一起构成营养不良聚糖复合体，后者结合层粘连蛋白-2，层粘连蛋白-2是雪旺细胞基底膜的主要成分。为了探讨周围神经营养不良多糖复合体与层粘连蛋白-2相互作用的生物学功能，研究了β-营养不良聚糖和层粘连蛋白-α2链在大鼠坐骨神经轴突变性和再生过程中以及正常状态下的表达。在正常坐骨神经中，β-dystroglan胞浆区的免疫反应持续和选择性地定位于与基底膜相对的外(外轴突)膜下的雪旺细胞质。在轴突变性过程中与轴突失去接触的雪旺细胞中，β-dystroglan的表达逐渐下调，而在再生过程中，随着被膜的再生和髓鞘的形成，其表达逐渐上调。有趣的是，在轴突变性和再生过程中，β-dystroglan的表达总是局限于与基底膜相对的外膜下的雪旺细胞质。此外，在轴突退变和再生过程中，层粘连蛋白-α-2的免疫反应与β-营养不良聚糖的免疫反应大致平行，这表明β-营养不良聚糖和层粘连蛋白-α-2的表达是由雪旺细胞与轴突接触诱导和维持的。我们的结果表明，营养不良多糖复合体参与了雪旺细胞外膜与基底膜的粘连，并提示该营养不良聚糖复合体可能通过与层粘连蛋白-2的相互作用而在雪旺细胞包膜和髓鞘形成过程中发挥作用。

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.