Centre for Molecular Microbiology and Infection, Imperial College London, London SW7 2AZ, UK.
J Cell Sci. 2012 Jun 15;125(Pt 12):2825-30. doi: 10.1242/jcs.106583. Epub 2012 Mar 27.
The adaptor protein Nck has been shown to link receptor ligation to actin-based signalling in a diverse range of cellular events, such as changes in cell morphology and motility. It has also been implicated in phagocytosis. However, its molecular role in controlling actin remodelling associated with phagocytic uptake remains to be clarified. Here, we show that Nck, which is recruited to phagocytic cups, is required for Fcγ receptor (FcγR)- but not complement receptor 3 (CR3)-induced phagocytosis. Nck recruitment in response to FcγR ligation is mediated by the phosphorylation of tyrosine 282 and 298 in the ITAM motif in the cytoplasmic tail of the receptor. In the absence of FcγR phosphorylation, there is also no recruitment of N-WASP or Cdc42 to phagocytic cups. Nck promotes FcγR-mediated phagocytosis by recruiting N-WASP to phagocytic cups. Efficient phagocytosis, however, only occurs, if the CRIB domain of N-WASP can also interact with Cdc42. Our observations demonstrate that Nck and Cdc42 collaborate to stimulate N-WASP-dependent FcγR-mediated phagocytosis.
衔接蛋白 Nck 已被证实可将受体的配体与多种细胞事件（如细胞形态和运动的变化）中的基于肌动蛋白的信号联系起来。它也与吞噬作用有关。然而，其在控制与吞噬作用摄取相关的肌动蛋白重塑中的分子作用仍有待阐明。在这里，我们表明，募集到吞噬杯中衔接蛋白 Nck 是 Fcγ 受体（FcγR）而不是补体受体 3（CR3）诱导的吞噬作用所必需的。受体胞质尾部 ITAM 基序中酪氨酸 282 和 298 的磷酸化介导了 FcγR 配体结合后 Nck 的募集。在没有 FcγR 磷酸化的情况下，N-WASP 和 Cdc42 也不会募集到吞噬杯中。Nck 通过将 N-WASP 募集到吞噬杯中促进 FcγR 介导的吞噬作用。然而，如果 N-WASP 的 CRIB 结构域也可以与 Cdc42 相互作用，才能有效地发生吞噬作用。我们的观察结果表明，Nck 和 Cdc42 协同作用来刺激依赖于 N-WASP 的 FcγR 介导的吞噬作用。
