Nck and Cdc42 co-operate to recruit N-WASP to promote FcγR-mediated phagocytosis
Nck and Cdc42 co-operate to recruit N-WASP to promote FcγR-mediated phagocytosis
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DOI：
10.1242/jcs.106583
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发表时间：
2012-06-15
影响因子：
4
通讯作者：
Caron, Emmanuelle
中科院分区：
文献类型：
--
作者：
Dart, Anna E.;Donnelly, Sara K.;Caron, Emmanuelle
接头蛋白Nck已被证明在多种细胞事件中，如细胞形态和运动的变化，将受体连接与基于肌动蛋白的信号传导联系起来。它也与吞噬作用有关。然而，其在控制与吞噬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，我们发现Nck被招募到吞噬杯中，是Fc γ受体（Fc γ R）所必需的，但不是补体受体3 （CR3）诱导的吞噬。受体胞质尾部ITAM基序中酪氨酸282和298的磷酸化介导了Fc γ R连接的Nck募集。在没有Fc γ R磷酸化的情况下，也没有N-WASP或Cdc42募集到吞噬杯。Nck通过将N-WASP招募到吞噬杯中来促进Fc γ r介导的吞噬作用。然而，只有当N-WASP的CRIB结构域也能与Cdc42相互作用时，才会发生有效的吞噬作用。我们的观察表明，Nck和Cdc42协同刺激n - wasp依赖的Fc γ r介导的吞噬作用。
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 Fc gamma receptor (Fc gamma R)-but not complement receptor 3 (CR3)-induced phagocytosis. Nck recruitment in response to Fc gamma R 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 Fc gamma R phosphorylation, there is also no recruitment of N-WASP or Cdc42 to phagocytic cups. Nck promotes Fc gamma R-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 Fc gamma R-mediated phagocytosis.