The p75 receptor acts as a displacement factor that releases Rho from Rho-GDI
The p75 receptor acts as a displacement factor that releases Rho from Rho-GDI
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DOI：
10.1038/nn1045
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发表时间：
2003-05-01
影响因子：
25
通讯作者：
Tohyama, M
中科院分区：
文献类型：
--
作者：
Yamashita, T;Tohyama, M
神经营养蛋白受体p75（NTR）参与神经营养蛋白以及几种髓鞘组分（包括Nogo、髓鞘相关糖蛋白（MAG）和髓鞘少突胶质细胞糖蛋白（OMgp））对轴突伸长的调节。神经营养因子通过抑制Rho活性刺激神经突生长，而髓磷脂衍生蛋白激活RhoA，从而抑制生长。在这里，我们表明，Rho GDP解离抑制剂（Rho-GDI）与p75（NTR）的直接相互作用启动了RhoA的激活，而MAG或Nogo加强了p75（NTR）和Rho-GDI之间的这种相互作用。我们还发现p75（NTR）促进异戊二烯化RhoA从Rho-GDI的释放。与p75第五个α螺旋（NTR）相关的肽配体抑制Rho-GDI和p75（NTR）之间的相互作用，从而沉默p75（NTR）介导的作用。该肽具有作为治疗剂对抗阻断中枢神经系统再生的抑制性信号的潜力。
The neurotrophin receptor p75(NTR) is involved in the regulation of axonal elongation by neurotrophins as well as several myelin components, including Nogo, myelin-associated glycoprotein (MAG) and myelin oligodendrocyte glycoprotein (OMgp). Neurotrophins stimulate neurite outgrowth by inhibiting Rho activity, whereas myelin-derived proteins activate RhoA and thereby inhibit growth. Here we show that direct interaction of the Rho GDP dissociation inhibitor (Rho-GDI) with p75(NTR) initiates the activation of RhoA, and this interaction between p75(NTR) and Rho-GDI is strengthened by MAG or Nogo. We also found that p75(NTR) facilitates the release of prenylated RhoA from Rho-GDI. The peptide ligand that is associated with the fifth alpha helix of p75(NTR) inhibits the interaction between Rho-GDI and p75(NTR), thus silencing the action mediated by p75(NTR). This peptide has potential as a therapeutic agent against the inhibitory cues that block regeneration in the central nervous system.