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

可溶性髓磷脂相关糖蛋白与特定神经节苷脂的结合诱导 p75NTR 与脂筏和信号转导的关联

• 批准号: 14570590
• 负责人: YASUDA Hitomi
• 金额: $ 2.5万
• 依托单位: Shiga University of Medical Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570590/
• 关键词: Ganglioside knockout mice; cerebellar granular cells; Inhibition of neurite outgrowth; MAG; Nogo,; RhoA; Lipid raft; p75NTR; GalNac Traferase; ノックアウトマウス; 神経突起進展; Rho A; lipid microdoin; GalNac Transferase; 低親和性ニューロトロフィン受容体; RhoA; lipid mic

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.

髓鞘相关包被糖蛋白（MAG）是一种有效的神经元突起生长抑制剂。膜结合形式的MAG的结合伴侣被证明是Nogo受体。在这里，我们表明，神经节苷脂，GT 1b和GD 1a，是可溶性MAG-Fc的功能性结合伴侣。来自GalNacT基因缺陷小鼠的出生后小脑神经元在神经突生长方面对MAG不敏感，并且缺乏RhoA的激活。MAG-Fc或针对GT 1b和GD 1a的抗体引发p75 NTR向脂筏的募集，脂筏是用于信号转导的专门微结构域。脂筏的破坏导致MAG-Fc以及Nogo肽的抑制作用的消除。这些发现表明神经节苷脂是可溶性MAG的功能性结合伴侣，神经节苷脂可能在p75 NTR转运至脂筏启动信号转导中发挥作用。