Cell adhesion molecules NgCAM and axonin-1 form heterodimers in the neuronal membrane and cooperate in neurite outgrowth promotion
Cell adhesion molecules NgCAM and axonin-1 form heterodimers in the neuronal membrane and cooperate in neurite outgrowth promotion
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DOI：
10.1083/jcb.135.6.1593
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发表时间：
1996-12-01
影响因子：
7.8
通讯作者：
Sonderegger, P
中科院分区：
文献类型：
--
作者：
Buchstaller, A;Kunz, S;Sonderegger, P
轴突表面糖蛋白神经元-神经胶质细胞黏附分子(NgCAM)和轴索素-1促进细胞与细胞的黏附、突起生长和丛生，并参与生长锥的引导。利用分离的分子结合到荧光微球的表面，证明了NgCAM与轴索素-1之间的直接结合。通过在骨髓瘤细胞中表达NgCAM和Axtin-1，并进行细胞聚集实验，我们发现NgCAM和Axtin-1存在于不同细胞的表面时不能结合。而在低密度培养的背根神经节细胞中，在抗体诱导下共表达NgCAM和NgCAM的CV-1细胞表面AX-1的共同封端和两个分子的选择性化学交联，表明AX-1和NgCAM在同一膜平面上发生了特异性的直接结合。通过反义寡核苷酸抑制Axin-1的翻译，阻止了在NgCAM底物上培养的分离的背根神经节神经元突起的生长，表明NgCAM底物上的神经突起生长需要AXIN-1。基于这些和以前的结果，暗示NgCAM是参与NgCAM底物上神经突起生长的神经元受体，我们得出结论，NgCAM底物上的神经突起生长依赖于生长锥NgCAM的两个基本相互作用：与NgCAM底物的反式相互作用和与位于同一生长锥膜中的Axtin-1的顺式相互作用。
The axonal surface glycoproteins neuron-glia cell adhesion molecule (NgCAM) and axonin-1 promote cell-cell adhesion, neurite outgrowth and fasciculation, and are involved in growth cone guidance. A direct binding between NgCAM and axonin-1 has been demonstrated using isolated molecules conjugated to the surface of fluorescent microspheres. By expressing NgCAM and axonin-1 in myeloma cells and performing cell aggregation assays, we found that NgCAM and axonin-1 cannot bind when present on the surface of different cells. In contrast, the cocapping of axonin-1 upon antibody-induced capping of NgCAM on the surface of CV-1 cells coexpressing NgCAM and axonin-1 and the selective chemical cross-linking of the two molecules in low density cultures of dorsal root ganglia neurons indicated a specific and direct binding of axonin-1 and NgCAM in the plane of the same membrane. Suppression of the axonin-1 translation by antisense oligonucleotides prevented neurite outgrowth in dissociated dorsal root ganglia neurons cultured on an NgCAM substratum, indicating that neurite outgrowth on NgCAM substratum requires axonin-1, Based on these and previous results, which implicated NgCAM as the neuronal receptor involved in neurite outgrowth on NgCAM substratum, we concluded that neurite outgrowth on an NgCAM substratum depends on two essential interactions of growth cone NgCAM: a trans-interaction with substratum NgCAM and a cis-interaction with axonin-1 residing in the same growth cone membrane.