Lieberoth Annika, Splittstoesser Frauke, Katagihallimath Nainesh, Jakovcevski Igor, Loers Gabriele, Ranscht Barbara, Karagogeos Domna, Schachner Melitta, Kleene Ralf
Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
J Neurosci. 2009 May 20;29(20):6677-90. doi: 10.1523/JNEUROSCI.4361-08.2009.
Although carbohydrates have been implicated in cell interactions in the nervous system, the molecular bases of their functions have remained largely obscure. Here, we show that promotion or inhibition of neurite outgrowth of cerebellar or dorsal root ganglion neurons, respectively, induced by the mucin-type adhesion molecule CD24 depends on alpha2,3-linked sialic acid and Lewis(x) present on glia-specific CD24 glycoforms. Alpha2,3-sialyl residues of CD24 bind to a structural motif in the first fibronectin type III domain of the adhesion molecule L1. Following the observation that the adhesion molecules TAG-1 and Contactin show sequence homologies with fucose-specific lectins, we obtained evidence that TAG-1 and Contactin mediate Lewis(x)-dependent CD24-induced effects on neurite outgrowth. Thus, L1, TAG-1, and Contactin function as lectin-like neuronal receptors. Their cis interactions with neighboring adhesion molecules, e.g., Caspr1 and Caspr2, and with their triggered signal transduction pathways elicit cell type-specific promotion or inhibition of neurite outgrowth induced by glial CD24 in a glycan-dependent trans interaction.
尽管碳水化合物已被认为与神经系统中的细胞相互作用有关，但其功能的分子基础在很大程度上仍不清楚。在此，我们表明，黏蛋白型黏附分子CD24分别诱导的小脑或背根神经节神经元轴突生长的促进或抑制，取决于神经胶质细胞特异性CD24糖型上存在的α2,3连接的唾液酸和Lewis(x)。CD24的α2,3-唾液酸残基与黏附分子L1的第一个III型纤连蛋白结构域中的一个结构基序结合。在观察到黏附分子TAG-1和Contactin与岩藻糖特异性凝集素具有序列同源性之后，我们获得了证据表明TAG-1和Contactin介导Lewis(x)依赖性CD24对轴突生长的诱导作用。因此，L1、TAG-1和Contactin作为类凝集素神经元受体发挥作用。它们与相邻黏附分子（如Caspr1和Caspr2）的顺式相互作用，以及与其触发的信号转导途径，在聚糖依赖性反式相互作用中引发神经胶质细胞CD24诱导的轴突生长的细胞类型特异性促进或抑制。
