The LIS1/NDE1 Complex Is Essential for FGF Signaling by Regulating FGF Receptor Intracellular Trafficking
The LIS1/NDE1 Complex Is Essential for FGF Signaling by Regulating FGF Receptor Intracellular Trafficking
复制标题
LIS1/NDE1 复合物通过调节 FGF 受体细胞内运输对 FGF 信号传导至关重要。
DOI：
10.1016/j.celrep.2018.02.077
复制
发表时间：
2018-03-20
期刊：
影响因子：
8.8
通讯作者：
Song, Hai
中科院分区：
文献类型：
--
作者：
Liu, Liansheng;Lu, Jinqiu;Song, Hai
细胞膜细胞器和蛋白质复合物到不同目的地的细胞内运输是信号转导和细胞功能的基础。细胞质动力蛋白马达及其调节蛋白LIS1和NDE1是沿着微管网络运输各种细胞货物所必需的。在这项研究中，我们发现在发育中的肺内胚层和肢体间充质细胞中缺失Lis1会导致肺和肢体发育不全。在这两种突变体中，细胞死亡增加，成纤维细胞生长因子（FGF）信号活性降低。在机制上，LIS1及其相互作用蛋白NDE1/NDEL1与含FGF受体的囊泡相关，并调节FGF受体在细胞内的运输和降解。值得注意的是，FGF信号传导促进NDE1酪氨酸磷酸化，从而导致LIS1/NDE1复合物的解离。因此，我们的研究确定了LIS1/NDE1复合物是一个重要的FGF信号调节因子，并为胞吞作用的细胞信号和运输机制的双向调节提供了见解。
Intracellular transport of membranous organelles and protein complexes to various destinations is fundamental to signaling transduction and cellular function. The cytoplasmic dynein motor and its regulatory proteins LIS1 and NDE1 are required for transporting a variety of cellular cargos along the microtubule network. In this study, we show that deletion of Lis1 in developing lung endoderm and limb mesenchymal cells causes agenesis of the lungs and limbs. In both mutants, there is increased cell death and decreased fibroblast growth factor (FGF) signaling activity. Mechanistically, LIS1 and its interacting protein NDE1/NDEL1 are associated with FGF receptor-containing vesicles and regulate FGF receptor intracellular trafficking and degradation. Notably, FGF signaling promotes NDE1 tyrosine phosphorylation, which leads to dissociation of LIS1/NDE1 complex. Thus, our studies identify the LIS1/NDE1 complex as an important FGF signaling regulator and provide insights into the bidirectional regulation of cell signaling and transport machinery for endocytosis.