Retention of a cell adhesion complex at the paranodal junction requires the cytoplasmic region of Caspr.
Retention of a cell adhesion complex at the paranodal junction requires the cytoplasmic region of Caspr.
复制标题
保留细胞粘附复合物在偏阳连接处需要CASPR的细胞质区域。
DOI：
10.1083/jcb.200203050
复制
发表时间：
2002-06-24
影响因子：
7.8
通讯作者：
Peles, Elior
中科院分区：
文献类型：
--
作者：
Gollan, Leora;Sabanay, Helena;Poliak, Sebastian;Berglund, Erik O;Ranscht, Barbara;Peles, Elior
细胞黏附分子的轴突复合体由CASPR和Conactin组成，对Rannvier结旁结旁轴突-神经胶质连接的产生是必不可少的。在这里，我们报告说，尽管CASPR的胞外区域足以将其导向转基因小鼠的偏阳极，但CASPR-Conactin复合体在连接处的保留取决于CASPR细胞质结构域的存在。利用免疫电子显微镜，我们发现CASPR突变体缺乏细胞内结构域，通常发现在轴突内，而不是在连接轴膜内。我们进一步证明，CASPR胞浆结构域中的一个短序列介导了它与细胞骨架相关蛋白4.1B的结合。接触蛋白在细胞表面的聚集导致CASPR和固定蛋白4.1B在质膜上的共同聚集。此外，蛋白4.1B结合位点的缺失加速了CASPR-Contact嵌合体从细胞表面的内化。这些结果表明，CASPR是一种“跨膜支架”，通过将CASPR/Conactin黏附复合体连接到轴突内的细胞骨架成分来稳定结旁交界处的黏附复合体。
An axonal complex of cell adhesion molecules consisting of Caspr and contactin has been found to be essential for the generation of the paranodal axo-glial junctions flanking the nodes of Ranvier. Here we report that although the extracellular region of Caspr was sufficient for directing it to the paranodes in transgenic mice, retention of the Caspr–contactin complex at the junction depended on the presence of an intact cytoplasmic domain of Caspr. Using immunoelectron microscopy, we found that a Caspr mutant lacking its intracellular domain was often found within the axon instead of the junctional axolemma. We further show that a short sequence in the cytoplasmic domain of Caspr mediated its binding to the cytoskeleton-associated protein 4.1B. Clustering of contactin on the cell surface induced coclustering of Caspr and immobilized protein 4.1B at the plasma membrane. Furthermore, deletion of the protein 4.1B binding site accelerated the internalization of a Caspr–contactin chimera from the cell surface. These results suggest that Caspr serves as a “transmembrane scaffold” that stabilizes the Caspr/contactin adhesion complex at the paranodal junction by connecting it to cytoskeletal components within the axon.