Binding of soluble myelin associated glycoprotein to specific gangliosides induces the association of p75NTR to lipid rafts and signal transduction

髓鞘包被糖蛋白(MAG)是一种有效的抑制多种神经元突起生长的物质。膜结合型MAG的结合伙伴是Nogo受体。在这里，我们证明了神经节苷脂GT1b和GD1a是可溶性MAG-Fc的功能性结合伙伴。GalNacT基因缺陷的小鼠生后小脑神经元对MAG不敏感，对突起生长和RhoA缺乏激活。MAG-Fc或抗GT1b和GD1a的抗体诱导p75NTR重新聚集到脂筏上，脂筏是信号转导的专门微域。破坏脂筏会导致MAG-Fc和Nogo肽的抑制作用丧失。这些发现确立了神经节苷脂作为可溶性MAG的功能性结合伙伴。神经节苷脂可能在p75NTR转位到脂筏启动信号转导中起作用。

Myelin-assocoated glycoprotein (MAG) is a potent inhibitor of neurite outgrowth from a variety of neurons. The binding partner for membrane-bound form of MAG is shown to be the Nogo receptor. Here we show that gangliosides, GT1b and GD1a, are functional binding partners for soluble MAG-Fc. Postnatal cerebellar neurons from mice deficient in the GalNacT gene are insensitive to MAG with regard to neurite outgrowth and lack in the activation of RhoA. MAG-Fc or the antibody to GT1b and GD1a elicites recruitment of p75NTR to lipid rafts, specialized microdomain for signal transduction. Disruption of lipid rafts results in abolishment of inhibitory effect of MAG-Fc as well as the Nogo peptide. These findings establish gangliosides as functional binding partner for soluble MAG. Gangliosides may play a role in translocation of p75 NTR to lipid rafts for initiation of the signal transduction.