Bacterial actin assembly requires toca-1 to relieve N-wasp autoinhibition

Cell Host Microbe. 2008 Jan 17;3(1):39-47. doi: 10.1016/j.chom.2007.10.011.


Actin polymerization in the mammalian cytosol can be locally activated by mechanisms that relieve the autoinhibited state of N-WASP, an initiator of actin assembly, a process that also requires the protein Toca-1. Several pathogenic bacteria, including Shigella, exploit this host feature to infect and disseminate efficiently. The Shigella outer membrane protein IcsA recruits N-WASP, which upon activation at the bacterial surface mediates localized actin polymerization. The molecular role of Toca-1 in N-WASP activation during physiological or pathological actin assembly processes in intact mammalian cells remains unclear. We show that actin tail initiation by S. flexneri requires Toca-1 for the conversion of N-WASP from a closed inactive conformation to an open active one. While N-WASP recruitment is dependent on IcsA, Toca-1 recruitment is instead mediated by S. flexneri type III secretion effectors. Thus, S. flexneri independently hijacks two nodes of the N-WASP actin assembly pathway to initiate localized actin tail assembly.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actins / metabolism*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation
  • HeLa Cells
  • Humans
  • Movement
  • Polymers / metabolism
  • Shigella flexneri / genetics
  • Shigella flexneri / metabolism
  • Shigella flexneri / pathogenicity*
  • Shigella flexneri / physiology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Wiskott-Aldrich Syndrome Protein, Neuronal / antagonists & inhibitors*
  • Wiskott-Aldrich Syndrome Protein, Neuronal / genetics
  • Wiskott-Aldrich Syndrome Protein, Neuronal / metabolism*


  • Actins
  • Bacterial Proteins
  • Carrier Proteins
  • DNA-Binding Proteins
  • FNBP1L protein, human
  • Polymers
  • Transcription Factors
  • Wiskott-Aldrich Syndrome Protein, Neuronal
  • virG protein, Shigella flexneri