MAP kinase pathway-dependent phosphorylation of the L1-CAM ankyrin binding site regulates neuronal growth.
MAP kinase pathway-dependent phosphorylation of the L1-CAM ankyrin binding site regulates neuronal growth.
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L1-CAM 锚蛋白结合位点的 MAP 激酶途径依赖性磷酸化调节神经元生长。
DOI：
10.1091/mbc.e06-01-0090
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发表时间：
2006
影响因子：
3.3
通讯作者：
Felsenfeld,DanP
中科院分区：
文献类型：
--
作者：
Whittard,JohnD;Sakurai,Takeshi;Cassella,MelanieR;Gazdoiu,Mihaela;Felsenfeld,DanP
神经元突起的生长关键取决于将细胞外配体连接到细胞骨架的粘附蛋白的功能。神经元粘附蛋白L1-CAM作为神经生长促进蛋白的受体，该过程被L1-CAM和细胞骨架适配器锚蛋白之间的相互作用抑制。使用一种新的报告分子内生物发光共振能量转移的基础上，我们已经确定，MAP激酶途径调节的FIGQY基序的磷酸化的粘附蛋白L1-CAM及其与锚蛋白B的相互作用。MAP激酶通路抑制剂阻断L1-CAM介导的神经元生长。然而，L1-CAM-锚蛋白结合的抑制剂部分地挽救了这种阻断。这些结果表明，MAP激酶途径通过调节锚蛋白结合来调节L1-CAM介导的神经生长，表明神经生长可以在单个受体水平上调节。
The growth of neuronal processes depends critically on the function of adhesion proteins that link extracellular ligands to the cytoskeleton. The neuronal adhesion protein L1-CAM serves as a receptor for nerve growth–promoting proteins, a process that is inhibited by the interaction between L1-CAM and the cytoskeleton adaptor ankyrin. Using a novel reporter based on intramolecular bioluminescence resonance energy transfer, we have determined that the MAP kinase pathway regulates the phosphorylation of the FIGQY motif in the adhesion protein L1-CAM and its interaction with ankyrin B. MAP kinase pathway inhibitors block L1-CAM–mediated neuronal growth. However, this blockade is partially rescued by inhibitors of L1-CAM–ankyrin binding. These results demonstrate that the MAP kinase pathway regulates L1-CAM–mediated nerve growth by modulating ankyrin binding, suggesting that nerve growth can be regulated at the level of individual receptors.