A central role for Necl4 ( SynCAM4) in Schwann cell- axon interaction and myelination
A central role for Necl4 ( SynCAM4) in Schwann cell- axon interaction and myelination
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DOI：
10.1038/nn1915
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发表时间：
2007-07-01
影响因子：
25
通讯作者：
Peles, Elior
中科院分区：
文献类型：
--
作者：
Spiegel, Ivo;Adamsky, Konstantin;Peles, Elior
外周神经系统的髓鞘形成需要雪旺细胞和轴突之间的密切接触，但其潜在的分子基础在很大程度上仍然未知。本研究表明，细胞粘附分子（CAMs）的连接蛋白样（Necl，也称为SynCAM或Cadm）家族在髓鞘形成过程中介导雪旺细胞-轴突相互作用。Necl4是髓鞘雪旺细胞表达的主要Necl，位于淋巴结间，与定位于轴突的Necl1直接相邻。Necl4作为轴突Necl1的胶质结合伙伴，这两个cam之间的相互作用介导了雪旺细胞的粘附。通过可溶性胞外结构域破坏Necl1和Necl4之间的相互作用，或在雪旺细胞中表达显性阴性Necl4，抑制髓鞘形成。这些结果表明，Necl蛋白在周围神经髓鞘形成过程中介导轴突-胶质细胞接触是重要的。
Myelination in the peripheral nervous system requires close contact between Schwann cells and the axon, but the underlying molecular basis remains largely unknown. Here we show that cell adhesion molecules (CAMs) of the nectin-like (Necl, also known as SynCAM or Cadm) family mediate Schwann cell-axon interaction during myelination. Necl4 is the main Necl expressed by myelinating Schwann cells and is located along the internodes in direct apposition to Necl1, which is localized on axons. Necl4 serves as the glial binding partner for axonal Necl1, and the interaction between these two CAMs mediates Schwann cell adhesion. The disruption of the interaction between Necl1 and Necl4 by their soluble extracellular domains, or the expression of a dominant-negative Necl4 in Schwann cells, inhibits myelination. These results suggest that Necl proteins are important for mediating axon-glia contact during myelination in peripheral nerves.