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）是一种有效的神经突生长抑制剂。MAG膜结合形式的结合伙伴被证明是Nogo受体。我们发现神经节苷脂GT1b和GD1a是可溶性MAG-Fc的功能性结合伙伴。缺乏GalNacT基因的小鼠出生后的小脑神经元在神经突生长和RhoA激活缺乏方面对MAG不敏感。MAG-Fc或GT1b和GD1a抗体诱导p75NTR募集到脂质筏上，这是信号转导的专门微域。脂筏的破坏导致MAG-Fc和Nogo肽的抑制作用的消除。这些发现证实神经节苷是可溶性MAG的功能性结合伙伴。神经节苷可能在p75 NTR向脂质筏的易位中发挥作用，从而启动信号转导。

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.