Whittard John D, Sakurai Takeshi, Cassella Melanie R, Gazdoiu Mihaela, Felsenfeld Dan P
Department of Pharmacology and Biological Chemistry, Mt. Sinai School of Medicine, New York, NY 10029, USA.
Mol Biol Cell. 2006 Jun;17(6):2696-706. doi: 10.1091/mbc.e06-01-0090. Epub 2006 Apr 5.
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.
神经元突起的生长关键取决于将细胞外配体与细胞骨架连接起来的黏附蛋白的功能。神经元黏附蛋白L1-CAM作为促进神经生长蛋白的受体，这一过程会受到L1-CAM与细胞骨架适配蛋白锚蛋白之间相互作用的抑制。利用基于分子内生物发光共振能量转移的新型报告基因，我们确定丝裂原活化蛋白激酶（MAP激酶）信号通路调节黏附蛋白L1-CAM中FIGQY基序的磷酸化及其与锚蛋白B的相互作用。MAP激酶信号通路抑制剂会阻断L1-CAM介导的神经元生长。然而，L1-CAM与锚蛋白结合的抑制剂可部分挽救这种阻断作用。这些结果表明，MAP激酶信号通路通过调节锚蛋白结合来调控L1-CAM介导的神经生长，这表明神经生长可在单个受体水平上得到调节。
