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N-WASP deficiency reveals distinct pathways for cell surface projections and microbial actin-based motility.

The Wiskott-Aldrich syndrome protein (WASP) family of molecules integrates upstream signalling events with changes in the actin cytoskeleton. N-WASP has been implicated both in the formation of cell-surface projections (filopodia) required for cell movement and in the actin-based motility of intracellular pathogens. To examine N-WASP function we have used homologous recombination to inactivate the gene encoding murine N-WASP. Whereas N-WASP-deficient embryos survive beyond gastrulation and initiate organogenesis, they have marked developmental delay and die before embryonic day 12. N-WASP is not required for the actin-based movement of the intracellular pathogen Listeria but is absolutely required for the motility of Shigella and vaccinia virus. Despite these distinct defects in bacterial and viral motility, N-WASP-deficient fibroblasts spread by using lamellipodia and can protrude filopodia. These results imply a crucial and non-redundant role for N-WASP in murine embryogenesis and in the actin-based motility of certain pathogens but not in the general formation of actin-containing structures.

Pubmed ID: 11584271


  • Snapper SB
  • Takeshima F
  • Antón I
  • Liu CH
  • Thomas SM
  • Nguyen D
  • Dudley D
  • Fraser H
  • Purich D
  • Lopez-Ilasaca M
  • Klein C
  • Davidson L
  • Bronson R
  • Mulligan RC
  • Southwick F
  • Geha R
  • Goldberg MB
  • Rosen FS
  • Hartwig JH
  • Alt FW


Nature cell biology

Publication Data

October 3, 2001

Associated Grants

  • Agency: NIAID NIH HHS, Id: R01 AI023262
  • Agency: NIAID NIH HHS, Id: R01 AI034276

Mesh Terms

  • Actins
  • Animals
  • Cell Line
  • Cell Line, Transformed
  • Cell Movement
  • Cell Surface Extensions
  • Embryonic and Fetal Development
  • Fibroblasts
  • Gene Targeting
  • Listeria
  • Mice
  • Microscopy, Fluorescence
  • Nerve Tissue Proteins
  • Platelet-Derived Growth Factor
  • Recombination, Genetic
  • Shigella flexneri
  • Vaccinia virus
  • Wiskott-Aldrich Syndrome Protein, Neuronal