1] MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK [2] Institute of Structural and Molecular Biology, University College London &Birkbeck College, London WC1E 6BT, UK.
Institute of Structural and Molecular Biology, University College London &Birkbeck College, London WC1E 6BT, UK.
Nature. 2015 Jan 22;517(7535):460-5. doi: 10.1038/nature14067. Epub 2014 Dec 17.
Endocytosis is required for internalization of micronutrients and turnover of membrane components. Endophilin has been assigned as a component of clathrin-mediated endocytosis. Here we show in mammalian cells that endophilin marks and controls a fast-acting tubulovesicular endocytic pathway that is independent of AP2 and clathrin, activated upon ligand binding to cargo receptors, inhibited by inhibitors of dynamin, Rac, phosphatidylinositol-3-OH kinase, PAK1 and actin polymerization, and activated upon Cdc42 inhibition. This pathway is prominent at the leading edges of cells where phosphatidylinositol-3,4-bisphosphate-produced by the dephosphorylation of phosphatidylinositol-3,4,5-triphosphate by SHIP1 and SHIP2-recruits lamellipodin, which in turn engages endophilin. This pathway mediates the ligand-triggered uptake of several G-protein-coupled receptors such as α2a- and β1-adrenergic, dopaminergic D3 and D4 receptors and muscarinic acetylcholine receptor 4, the receptor tyrosine kinases EGFR, HGFR, VEGFR, PDGFR, NGFR and IGF1R, as well as interleukin-2 receptor. We call this new endocytic route fast endophilin-mediated endocytosis (FEME).
内吞作用是细胞内化微量营养素和膜成分更新所必需的。内吞素被认为是网格蛋白介导的内吞作用的一个组成部分。在这里，我们在哺乳动物细胞中表明，内吞素标记并控制一种快速作用的小管泡状内吞途径，该途径独立于 AP2 和网格蛋白，在配体与货物受体结合时被激活，被肌球蛋白抑制剂、Rac、磷脂酰肌醇-3-羟基激酶、PAK1 和肌动蛋白聚合抑制，在 Cdc42 抑制时被激活。该途径在细胞的前缘很明显，其中由SHIP1 和 SHIP2 对磷酸肌醇-3,4,5-三磷酸的去磷酸化产生的磷脂酰肌醇-3,4-二磷酸招募片状蛋白，片状蛋白反过来与内吞素结合。该途径介导了几种 G 蛋白偶联受体（如 α2a-和 β1-肾上腺素能受体、多巴胺 D3 和 D4 受体以及毒蕈碱乙酰胆碱受体 4）、受体酪氨酸激酶 EGFR、HGFR、VEGFR、PDGFR、NGFR 和 IGF1R 以及白细胞介素-2 受体的配体触发摄取。我们称这种新的内吞途径为快速内吞素介导的内吞作用（FEME）。
