The axonal membrane protein Caspr, a homologue of neurexin IV, is a component of the septate-like paranodal junctions that assemble during myelination.

The axonal membrane protein Caspr, a homologue of neurexin IV, is a component of the septate-like paranodal junctions that assemble during myelination.
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DOI:
10.1083/jcb.139.6.1495
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发表时间:
1997-12-15
影响因子:
7.8
通讯作者:
Salzer, JL
Salzer, JL
中科院分区:
生物学1区
文献类型:
--
作者:
Einheber, S;Zanazzi, G;Ching, W;Scherer, S;Milner, TA;Peles, E;Salzer, JL

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我们研究了联系蛋白和联系蛋白相关蛋白(CASPR)在髓鞘形成的轴突-神经胶质相互作用中的潜在作用。在神经系统中,接触蛋白由神经元、少突胶质细胞及其前体细胞表达,但不由雪旺细胞表达。CASPR是Neuresin IV的同系物,其表达仅限于神经元。在体外和体内髓鞘形成过程中,Contact n和CASPR均在无鞘神经突起表面高水平表达,并下调表达。在整个有髓神经纤维上,Contactin表达下调。相反,CASPR最初在与新生髓鞘相关的轴突片段上保持高表达。随着进一步的成熟,CASPR在节间下调,并显著集中在轴突的结旁区域,这表明它从节间重新分布到这些位置。CASPR的表达同样局限于周围和中枢神经系统中成熟的有髓轴突的副节点;它在灰质和无髓轴突中的表达更为广泛和持久。免疫电子显微镜显示CASPR定位于髓鞘细胞的轴突和结旁环之间形成的间隔状连接。CASPR被非离子洗涤剂提取得很差,这表明它与这些连接处的轴突细胞骨架有关。这些结果表明,Contactin和CASPR在髓鞘形成过程中独立发挥作用,其表达受神经胶质包膜的调节。它们强烈暗示CASPR是结旁连接的主要跨膜成分,其分子组成此前尚不清楚,并提示其在轴突和胶质细胞之间的相互信号传递中发挥作用。
We have investigated the potential role of contactin and contactin-associated protein (Caspr) in the axonal–glial interactions of myelination. In the nervous system, contactin is expressed by neurons, oligodendrocytes, and their progenitors, but not by Schwann cells. Expression of Caspr, a homologue of Neurexin IV, is restricted to neurons. Both contactin and Caspr are uniformly expressed at high levels on the surface of unensheathed neurites and are downregulated during myelination in vitro and in vivo. Contactin is downregulated along the entire myelinated nerve fiber. In contrast, Caspr expression initially remains elevated along segments of neurites associated with nascent myelin sheaths. With further maturation, Caspr is downregulated in the internode and becomes strikingly concentrated in the paranodal regions of the axon, suggesting that it redistributes from the internode to these sites. Caspr expression is similarly restricted to the paranodes of mature myelinated axons in the peripheral and central nervous systems; it is more diffusely and persistently expressed in gray matter and on unmyelinated axons. Immunoelectron microscopy demonstrated that Caspr is localized to the septate-like junctions that form between axons and the paranodal loops of myelinating cells. Caspr is poorly extracted by nonionic detergents, suggesting that it is associated with the axon cytoskeleton at these junctions. These results indicate that contactin and Caspr function independently during myelination and that their expression is regulated by glial ensheathment. They strongly implicate Caspr as a major transmembrane component of the paranodal junctions, whose molecular composition has previously been unknown, and suggest its role in the reciprocal signaling between axons and glia.
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发表时间: 1995-04
影响因子: 7.8
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