NEURONAL CELL CELL-ADHESION DEPENDS ON INTERACTIONS OF N-CAM WITH HEPARIN-LIKE MOLECULES
NEURONAL CELL CELL-ADHESION DEPENDS ON INTERACTIONS OF N-CAM WITH HEPARIN-LIKE MOLECULES
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DOI：
10.1038/320445a0
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发表时间：
1986-04-03
期刊：
影响因子：
64.8
通讯作者：
GLASER, L
中科院分区：
文献类型：
--
作者：
COLE, GJ;LOEWY, A;GLASER, L
细胞-细胞相互作用在神经发育过程中至关重要，特别是因为神经细胞的迁移和生长轴突与其靶细胞之间的功能性相互作用的建立1，2已被认为取决于细胞识别过程。神经元-神经元粘附已在体外得到了很好的研究，并且部分由神经细胞粘附分子N-CAM 3 -7介导。假设N-CAM介导的细胞间粘附通过嗜同性结合机制8发生，其中一个细胞表面上的N-CAM与相邻细胞上的N-CAM结合。我们实验室的研究已经确定了一种细胞表面糖蛋白，现在已知为N-CAM 9，其参与发育中的鸡神经系统中的细胞-基质相互作用10 -12。虽然这种粘附涉及嗜同性结合机制，但也需要细胞表面蛋白聚糖硫酸乙酰肝素与糖蛋白的结合13。这就提出了一个问题，即硫酸乙酰肝素与N-CAM的结合是否也是细胞-细胞粘附所必需的。在这里，我们表明，视网膜探针细胞的视网膜细胞单层的结合被抑制肝素，硫酸乙酰肝素的功能类似物，但不是由硫酸软骨素。识别N-CAM上的两个不同结构域（同型结合结构域和肝素结合结构域）的单克隆抗体可抑制细胞间粘附。通过选择性蛋白水解从N-CAM分离的肝素结合结构域在与探针细胞结合时也抑制细胞-细胞粘附。
Cell–cell interactions are of critical importance during neural development, particularly since the migration of neural cells and the establishment of functional interactions between growing axons and their target cells1,2has been suggested to depend upon cell recognition processes. Neurone–neurone adhesion has been well studiedin vitro, and is mediated in part by the neural cell adhesion molecule N-CAM3–7. N-CAM-mediated cell–cell adhesion has been postulated to occur by a homophilic binding mechanism8, in which N-CAM on the surface of one cell binds to N-CAM on a neighbouring cell. Studies in our laboratory have identified a cell surface glycoprotein, now known to be N-CAM9, which participates in cell–substratum interactions in the developing chicken nervous system10–12. Although this adhesion involves a homophilic binding mechanism, the binding of the cell surface proteoglycan heparan sulphate to the glycoprotein is also required13. This raises the question of whether the binding of heparan sulphate to N-CAM is also required for cell-cell adhesion. Here we show that the binding of retinal probe cells to retinal cell monolayers is inhibited by heparin, a functional analogue of heparan sulphate, but not by chondroitin sulphate. Monoclonal antibodies that recognize two different domains on N-CAM, the homophilic-binding and heparin-binding domains, inhibit cell–cell adhesion. The heparin-binding domain isolated from N-CAM by selective proteolysis also inhibits cell-cell adhesion when bound to the probe cells.