Neurofascin is a glial receptor for the paranodin/Caspr-contactin axonal complex at the axoglial junction
Neurofascin is a glial receptor for the paranodin/Caspr-contactin axonal complex at the axoglial junction
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DOI：
10.1016/s0960-9822(01)00680-7
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发表时间：
2002-02-05
期刊：
影响因子：
9.2
通讯作者：
Lubetzki, C
中科院分区：
文献类型：
--
作者：
Charles, P;Tait, S;Lubetzki, C
在脊椎动物神经系统的有髓纤维中，神经胶质鞘细胞与轴突在专门的粘附连接处相互作用，即结旁隔样连接处[1]。轴突蛋白paranodin/Caspr和contactin在轴胶质粘附区的轴膜中形成顺式复合物，并且两者都是稳定连接所必需的[2，3]。有强烈的猜测认为，在结旁环表达的细胞粘附分子神经成束蛋白的少突胶质细胞亚型NF 155 [4，5]可能是paranodin/Caspr-接触蛋白复合物的胶质细胞受体，特别是因为paranodin/Caspr和NF 155共定位于髓鞘发育不良小鼠Shiverer突变体CNS中的异位位点[5]。我们报告，NF 155的细胞外结构域特异性结合到在细胞表面表达paranodin/Caspr-contactin复合物的转染细胞。NF 155的该区域还在体外结合来自脑裂解物的paranodin/Caspr-接触蛋白复合物。为了支持这种相互作用的功能意义，NF 155抗体和NF 155的细胞外结构域抑制髓鞘形成共培养物中的髓鞘形成，推测是通过阻断轴突和神经胶质细胞之间的粘附关系。这些结果表明，paranodin/Caspr-contactin复合物与NF 155发生生物化学相互作用，并且这种相互作用可能与轴突神经连接处的生物学相关。
In myelinated fibers of the vertebrate nervous system, glial-ensheathing cells interact with axons at specialized adhesive junctions, the paranodal septate-like junctions [1]. The axonal proteins paranodin/Caspr and contactin form a cis complex in the axolemma at the axoglial adhesion zone, and both are required to stabilize the junction [2, 3]. There has been intense speculation that an oligodendroglial isoform of the cell adhesion molecule neurofascin, NF155, expressed at the paranodal loop [4,5] might be the glial receptor for the paranodin/Caspr-contactin complex, particularly since paranodin/Caspr and NF155 colocalize to ectopic sites in the CNS of the dysmyelinated mouse Shiverer mutant [5]. We report that the extracellular domain of NF155 binds specifically to transfected cells expressing the paranodin/Caspr-contactin complex at the cell surface. This region of NF155 also binds the paranodin/Caspr-contactin complex from brain lysates in vitro. In support of the functional significance of this interaction, NF155 antibodies and the extracellular domain of NF155 inhibit myelination in myelinating cocultures, presumably by blocking the adhesive relationship between the axon and glial cell. These results demonstrate that the paranodin/Caspr-contactin complex interacts biochemically with NF155 and that this interaction is likely to be biologically relevant at the axoglial junction.