Binding of soluble myelin-associated glycoprotein to specific gangliosides induces the association of p75NTR to lipid rafts and signal transduction
Binding of soluble myelin-associated glycoprotein to specific gangliosides induces the association of p75NTR to lipid rafts and signal transduction
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DOI：
10.1111/j.1471-4159.2005.03121.x
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发表时间：
2005-07-01
影响因子：
4.7
通讯作者：
Yamashita, T
中科院分区：
文献类型：
--
作者：
Fujitani, M;Kawai, H;Yamashita, T
髓鞘相关糖蛋白(MAG)是一种有效的抑制多种神经元突起生长的物质。在这里，我们发现神经节苷脂、GT1b和GD1a以及Nogo受体是可溶性MAG-Fc的功能性结合伙伴。来自GalNAcT基因缺陷的小鼠出生后的小脑神经元对MAG不敏感，对轴突生长和RhoA缺乏激活。MAG-Fc或抗GT1b和GD1a的抗体可引起p75(NTR.)对于脂筏，信号转导的专门微域。破坏脂筏导致MAG-Fc和Nogo肽的抑制作用消失。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p75(NTR)易位中起作用。至脂筏启动信号转导。
Myelin-associated glycoprotein (MAG) is a potent inhibitor of neurite outgrowth from a variety of neurons. Here we show that gangliosides, GT1b and GD1a, as well as the Nogo receptor, 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 elicits recruitment of p75(NTR.) to lipid rafts, specialized microdomain for signal transduction. Disruption of lipid rafts results in abolishment of inhibitory effects of MAG-Fc and the Nogo peptide. These findings establish gangliosides as functional binding partners for soluble MAG. Gangliosides may play a role in translocation of p75(NTR.) to lipid rafts for initiation of the signal transduction.