MOLECULAR MECHANISM OF PERIPHEARAL MYELINOGENESIS

在雪旺细胞中，跨膜糖蛋白β-三磷酸腺苷与结合雪旺细胞基底层主要成分层粘连蛋白-2的细胞外糖蛋白α-三磷酸腺苷一起构成了三磷酸腺苷复合物。为了进一步了解层粘连蛋白-2在周围神经中相互作用的生物学功能，我们研究了β-层粘连蛋白和层粘连蛋白-α2链在大鼠坐骨神经轴突变性和再生以及正常状态下的表达情况。在正常坐骨神经中，β-三磷酸腺苷胞质区域的免疫反应性一致且选择性地定位于靠近基底板的外（轴突）膜下的雪旺氏细胞质。在与轴突失联的雪旺细胞中，β-异常糖聚糖的表达在轴突变性过程中逐渐下调，而在再生过程中，随着鞘层和髓鞘的再生过程的进行，β-异常糖聚糖的表达逐渐上调。有趣的是，在轴突变性和再生过程中，β-异常糖聚糖的表达，当检测到时，总是局限于雪旺细胞外膜下靠近基板的细胞质。此外，在轴突变性和再生过程中，层粘连蛋白-α2的免疫反应性与β-糖歧义蛋白的免疫反应性大致相似，表明β-糖歧义蛋白和层粘连蛋白-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糖异常复合物参与了雪旺细胞外膜与基板的粘附，并提示糖异常复合物可能通过与层粘连蛋白-2的相互作用在雪旺细胞的鞘鞘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.