Nck and Cdc42 co-operate to recruit N-WASP to promote FcγR-mediated phagocytosis

J Cell Sci. 2012 Jun 15;125(Pt 12):2825-30. doi: 10.1242/jcs.106583. Epub 2012 Mar 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Motifs
  • Animals
  • Humans
  • Macrophages / metabolism
  • Mice
  • Mice, Knockout
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism*
  • Phagocytosis*
  • Protein Binding
  • Receptors, IgG / chemistry
  • Receptors, IgG / genetics
  • Receptors, IgG / metabolism*
  • Signal Transduction
  • Wiskott-Aldrich Syndrome / genetics
  • Wiskott-Aldrich Syndrome / metabolism*
  • Wiskott-Aldrich Syndrome / physiopathology
  • Wiskott-Aldrich Syndrome Protein, Neuronal / genetics
  • Wiskott-Aldrich Syndrome Protein, Neuronal / metabolism*
  • cdc42 GTP-Binding Protein / genetics
  • cdc42 GTP-Binding Protein / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Fc gamma receptor IIA
  • Nck protein
  • Oncogene Proteins
  • Receptors, IgG
  • Wiskott-Aldrich Syndrome Protein, Neuronal
  • cdc42 GTP-Binding Protein