Neural Wiskott-Aldrich syndrome protein (N-WASP) is the specific ligand for Shigella VirG among the WASP family and determines the host cell type allowing actin-based spreading

Cell Microbiol. 2002 Apr;4(4):223-33. doi: 10.1046/j.1462-5822.2002.00185.x.


Shigella, the causative agent of bacillary dysentery, is capable of directing its movement within host cells by forming an actin comet tail. The VirG (IcsA) pro-tein expressed at one pole of the bacterium recruits neural Wiskott-Aldrich syndrome protein (N-WASP), a member of the WASP family, which in turn stimulates actin-related protein (Arp) 2/3 complex-mediated actin polymerization. As all the WASP family proteins induce actin polymerization by recruiting Arp2/3 complex, we investigated their involvement in Shigella motility. Here, we show that VirG binds to N-WASP but not to the other WASP family proteins. Using a series of chimeras obtained by swapping N-WASP and WASP domains, we demonstrated that the specificity of VirG to interact with N-WASP lies in the N-terminal region containing the pleckstrin homology (PH) domain and calmodulin-binding IQ motif of N-WASP. A conformational change in N-WASP was important for the VirG-N-WASP interaction, as elimination of the C-terminal acidic region, which is responsible for the intramolecular interaction with the central basic region of N-WASP, affected the specific binding to VirG. We observed that, in haematopoietic cells such as macrophages, polymorphonuclear leucocytes (PMNs) and platelets, WASP was predominantly expressed, whereas the expression of N-WASP was greatly suppressed. Indeed, unlike Listeria, Shigella was unable to move in macrophages at all, although the movement was restored as N-WASP was expressed ectopically. Thus, our findings demonstrate that N-WASP is a specific ligand of VirG, which determines the host cell type allowing actin-based spreading of Shigella.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / chemistry
  • Actins / metabolism*
  • Bacterial Proteins
  • Biological Transport
  • Cells, Cultured
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Ligands
  • Macrophages / metabolism
  • Macrophages / microbiology
  • Nerve Tissue Proteins / metabolism*
  • Shigella / metabolism*
  • Signal Transduction
  • Transcription Factors / metabolism*
  • Wiskott-Aldrich Syndrome Protein, Neuronal


  • Actins
  • Bacterial Proteins
  • DNA-Binding Proteins
  • Ligands
  • Nerve Tissue Proteins
  • Transcription Factors
  • WASL protein, human
  • Wiskott-Aldrich Syndrome Protein, Neuronal
  • virG protein, Shigella flexneri