Molecular composition of the node of Ranvier: identification of ankyrin-binding cell adhesion molecules neurofascin (mucin+/third FNIII domain-) and NrCAM at nodal axon segments.
Molecular composition of the node of Ranvier: identification of ankyrin-binding cell adhesion molecules neurofascin (mucin+/third FNIII domain-) and NrCAM at nodal axon segments.
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Ranvier节点的分子组成：在淋巴结段鉴定Ankyrin结合细胞粘附分子神经胶质素（粘蛋白+/第三FNIII结构域）和NRCAM。
DOI：
10.1083/jcb.135.5.1355
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发表时间：
1996-12
期刊：
影响因子：
--
通讯作者：
Bennett V
中科院分区：
文献类型：
--
作者：
Davis JQ;Lambert S;Bennett V
神经成束蛋白、NrCAM、L1和NgCAM是IG/FNIII细胞粘附分子家族，其在其胞质结构域中具有锚定结合活性，并且是在神经系统的多种细胞环境中与血影蛋白结合蛋白的锚蛋白家族成员形成跨膜复合物的候选者。锚蛋白的特殊形式，270 kD和/或480 kD的锚蛋白G是朗维尔结处轴突的膜底涂层的组分。本文着重于定义的亚型的粘附结合细胞粘附分子定位与ankrexG在节点轴突节段。通过分离全长cDNA确定两种主要形式的神经成束蛋白的外显子使用，并用于制备同种型特异性抗体。含有粘蛋白样结构域和缺乏第三个FNIII结构域的神经成束蛋白的亚型集中在轴突的初始段和共定位在节点的Ranvier与ankrelin G和电压依赖性钠通道。另一种形式的神经成束蛋白缺乏粘蛋白样结构域和含有第三FNIII结构域存在于无髓鞘轴突。最初针对神经成束蛋白产生的抗体用于筛选大鼠脑cDNA表达文库。除了神经成束蛋白，该筛选产生了与来自鸡的NrCAM具有80%序列同一性的克隆。提供了两个全长cDNA的序列。在L1/神经成束蛋白/NgCAM家族的其他成员中，NrCAM与神经成束蛋白最密切相关，在胞质结构域之间具有超过70%的同一性。NrCAM，可视化与抗体特异性的胞外结构域，也被发现与神经成束蛋白在节点的Ranvier和轴突起始段共表达。这是第一次表征定义的神经元细胞粘附分子定位于轴突膜在节点的Ranvier的有髓轴突。
Neurofascin, NrCAM, L1, and NgCAM are a family of Ig/FNIII cell adhesion molecules that share ankyrin-binding activity in their cytoplasmic domains, and are candidates to form membrane-spanning complexes with members of the ankyrin family of spectrin-binding proteins in a variety of cellular contexts in the nervous system. Specialized forms of ankyrin, 270 kD and/or 480 kD ankyrinG are components of the membrane undercoat of axons at the node of Ranvier. This paper focuses on definition of the isoforms of ankyrin-binding cell adhesion molecules localized with ankyrinG at the nodal axon segment. The exon usage of two major forms of neurofascin was determined by isolation of full-length cDNAs and used to prepare isoform-specific antibodies. An isoform of neurofascin containing a mucin-like domain and lacking the third FNIII domain was concentrated at axon initial segments and colocalized at nodes of Ranvier with ankyrinG and the voltage-dependent sodium channel. An alternative form of neurofascin lacking the mucin-like domain and containing the third FNIII domain was present in unmyelinated axons. The antibody initially raised against neurofascin was used to screen a rat brain cDNA expression library. In addition to neurofascin, this screen yielded a clone with 80% sequence identity to NrCAM from chicken. The sequences of two full-length cDNAs are presented. NrCAM is most closely related to neurofascin among the other members of the L1/neurofascin/NgCAM family, with over 70% identity between cytoplasmic domains. NrCAM, visualized with antibodies specific for the ecto-domain, also was found to be coexpressed with neurofascin at nodes of Ranvier and at axon initial segments. This is the first characterization of defined neuronal cell adhesion molecules localized to axonal membranes at the node of Ranvier of myelinated axons.