MAG induces regulated intramembrane proteolysis of the p75 neurotrophin receptor to inhibit neurite outgrowth
MAG induces regulated intramembrane proteolysis of the p75 neurotrophin receptor to inhibit neurite outgrowth
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DOI：
10.1016/j.neuron.2005.05.029
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发表时间：
2005-06-16
期刊：
影响因子：
16.2
通讯作者：
Filbin, MT
中科院分区：
文献类型：
--
作者：
Domeniconi, M;Zampieri, N;Filbin, MT
髓鞘质 MAG、Nogo 和 OMgp 中存在的三种已知的轴突再生抑制剂均与相同的受体复合物相互作用，通过蛋白激酶 C (PKC) 依赖性小 GTPase Rho 的激活来实现抑制。该受体复合物的转导成分是 p75 神经营养素受体。在这里，我们表明，MAG 与小脑神经元的结合会以蛋白激酶 C 依赖性方式诱导 p75 的 α 分泌酶和随后的 γ 分泌酶蛋白水解裂解，并且这种裂解对于 Rho 的激活和神经突生长的抑制都是必需的。
The three known inhibitors of axonal regeneration present in myelin-MAG, Nogo, and OMgp-all interact with the same receptor complex to effect inhibition via protein kinase C (PKC)-dependent activation of the small GTPase Rho. The transducing component of this receptor complex is the p75 neurotrophin receptor. Here we show that MAG binding to cerebellar neurons induces alpha- and then gamma-secretase proteolytic cleavage of p75, in a protein kinase C-dependent manner, and that this cleavage is necessary for both activation of Rho and inhibition of neurite outgrowth.