title: Nck and Cdc42 co-operate to recruit N-WASP to promote FcγR-mediated phagocytosis.
abstract: 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.
authors.affiliation: Centre for Molecular Microbiology and Infection, Imperial College London, London SW7 2AZ,  UK.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Dart
authors.forename: Sara K
authors.initials: SK
authors.lastname: Donnelly
authors.forename: David W
authors.initials: DW
authors.lastname: Holden
authors.forename: Michael
authors.initials: M
authors.lastname: Way
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Caron
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs; D000818:Animals; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D010587:Phagocytosis; D011485:Protein Binding; D017452:Receptors, IgG / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000235:genetics / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C080568:Fc gamma receptor IIA; C078332:Nck protein; D015513:Oncogene Proteins; D017452:Receptors, IgG; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D020764:cdc42 GTP-Binding Protein