Walsh F S, Doherty P
Department of Experimental Pathology, UMDS, Guy's Hospital, London.
Cell Biol Int Rep. 1991 Nov;15(11):1151-66. doi: 10.1016/0309-1651(91)90061-m.
A large number of glycoproteins in the central nervous system are attached to the cell membrane via covalent linkage to glycosylphosphatidylinositol (GPI). Many of them, including the drosophila fasciclin 1 as well as the mammalian glycoproteins Thy-1, TAG1, N-CAM and F11,F3, contactin are members of the immunoglobulin gene superfamily. These and other GPI-linked molecules have been implicated in key developmental events including selective axonal fasciculation and highly specific growth to and innervation of target tissues. In model systems fasciclin 1, TAG1 and N-CAM have been shown to be capable of mediating cell-cell adhesion via a homophilic binding mechanism confirming their operational classification as cell adhesion molecules (CAMs). However, of these molecules, only N-CAM has been shown to mediate a complex response (neurite outgrowth) via a homophilic binding mechanism. Whether the other molecules in this family mediate biological responses by binding to themselves and/or other molecules remains to be determined. Studies on N-CAM provide an ideal model system for understanding the function of GPI anchors since alternative splicing of the NCAM gene generates both lipid-linked and transmembrane N-CAM isoforms. Recent studies have shown that neurons can recognise and respond (by increased neurite outgrowth) to both lipid-linked and transmembrane N-CAM isoforms expressed on the surface of non-neuronal cells following transfection with appropriate cDNAs. The major determinant of neuronal responsiveness was the level of N-CAM expression rather than the isoform type. Neurite outgrowth in response to transfected N-CAM is mediated by transmembrane N-CAM isoforms expressed by neurons and this involves the activation of classical second messenger pathways in the neurons. One possibility is that GPI anchors are utilised when a cell has simply to provide recognition or positional information to a second cell whereas transmembrane molecules might be required for cells that actively respond to such information. The hypothesis is compatible with all the known information on N-CAM expression and function and may be extended to other adhesive events.
中枢神经系统中的大量糖蛋白通过与糖基磷脂酰肌醇（GPI）的共价连接附着于细胞膜。其中许多糖蛋白，包括果蝇的成束蛋白1以及哺乳动物糖蛋白Thy-1、TAG1、N-CAM和F11、F3、接触蛋白，都是免疫球蛋白基因超家族的成员。这些以及其他GPI连接分子参与了关键的发育事件，包括选择性轴突成束以及向靶组织的高度特异性生长和神经支配。在模型系统中，成束蛋白1、TAG1和N-CAM已被证明能够通过同种型结合机制介导细胞间粘附，证实它们作为细胞粘附分子（CAMs）的功能分类。然而，在这些分子中，只有N-CAM已被证明能通过同种型结合机制介导复杂反应（神经突生长）。该家族中的其他分子是否通过与自身和/或其他分子结合来介导生物学反应仍有待确定。对N-CAM的研究为理解GPI锚的功能提供了一个理想的模型系统，因为NCAM基因的可变剪接产生了脂质连接和跨膜的N-CAM异构体。最近的研究表明，在用适当的cDNA转染后，神经元能够识别非神经元细胞表面表达的脂质连接和跨膜N-CAM异构体并做出反应（通过增加神经突生长）。神经元反应性的主要决定因素是N-CAM的表达水平而非异构体类型。对转染的N-CAM的神经突生长反应由神经元表达的跨膜N-CAM异构体介导，这涉及神经元中经典第二信使途径的激活。一种可能性是，当一个细胞只需向另一个细胞提供识别或位置信息时，就利用GPI锚，而对于积极响应此类信息的细胞可能需要跨膜分子。该假设与关于N-CAM表达和功能的所有已知信息相符，并且可能扩展到其他粘附事件。
