Oligodendrocytes assist in the maintenance of sodium channel clusters independent of the myelin sheath
Oligodendrocytes assist in the maintenance of sodium channel clusters independent of the myelin sheath
复制标题
DOI：
10.1017/s1740925x04000304
复制
发表时间：
2004-01-01
影响因子：
--
通讯作者：
Popko, Brian
中科院分区：
文献类型：
--
作者：
Dupree, Jeffrey L.;Mason, Jeffrey L.;Popko, Brian
为了确保快速和有效的冲动传导，有髓鞘轴突建立和维持特定的蛋白质结构域。例如，钠（Na（+））通道聚集在郎维氏结中;钾（K（+））通道聚集在旁阳极中的neurexin/caspr/paranodin簇中。我们的理解的机制，控制这些蛋白质的初始聚类是有限的，更少的是知道域维护。相关数据表明髓鞘形成和/或成熟髓鞘形成细胞介导所有三个结构域的形成。在这里，我们测试是否需要髓鞘维持钠（+）通道域的节点间隙采用两个脱髓鞘小鼠模型：（1）铜腙摄入，诱导完全脱髓鞘通过少突胶质细胞毒性;和（2）神经酰胺半乳糖基转移酶缺陷小鼠，经历自发性成人发病脱髓鞘没有少突胶质细胞死亡。我们的数据表明，髓鞘是必不可少的钠通道域的长期维护，然而，少突胶质细胞，独立于髓鞘，提供了部分保护性的影响，对节点Na（+）通道集群的维护。因此，我们提出多种机制调节节点蛋白组织的维持。最后，我们提出的证据表明，损失后的Na（+）通道集群的表达和重新集群的Na（+）通道亚型的CNS髓鞘再生过程中的时间进程重演的发展。
To ensure rapid and efficient impulse conduction, myelinated axons establish and maintain specific protein domains. For instance, sodium (Na(+)) channels accumulate in the node of Ranvier; potassium (K(+)) channels aggregate in the juxtaparanode and neurexin/caspr/paranodin clusters in the paranode. Our understanding of the mechanisms that control the initial clustering of these proteins is limited and less is known about domain maintenance. Correlative data indicate that myelin formation and/or mature myelin-forming cells mediate formation of all three domains. Here, we test whether myelin is required for maintaining Na(+) channel domains in the nodal gap by employing two demyelinating murine models: (1) cuprizone ingestion, which induces complete demyelination through oligodendrocyte toxicity; and (2) ceramide galactosyltransferase deficient mice, which undergo spontaneous adult-onset demyelination without oligodendrocyte death. Our data indicate that the myelin sheath is essential for long-term maintenance of sodium channel domains; however, oligodendrocytes, independent of myelin, provide a partial protective influence on the maintenance of nodal Na(+) channel clusters. Thus, we propose that multiple mechanisms regulate the maintenance Of nodal protein organization. Finally, we present evidence that following the loss of Na(+) channel clusters the chronological progression of expression and reclustering of Na(+) channel isoforms during the course of CNS remyelination recapitulates development.