title: N-WASP deficiency reveals distinct pathways for cell surface projections and microbial actin-based motility.
abstract: 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.
authors.affiliation: Center for Blood Research, 200 Longwood Avenue, Boston, Massachusetts 02115, USA. ssnapper@hms.harvard.edu
authors.forename: S B
authors.initials: SB
authors.lastname: Snapper
authors.forename: F
authors.initials: F
authors.lastname: Takeshima
authors.forename: I
authors.initials: I
authors.lastname: Antón
authors.forename: C H
authors.initials: CH
authors.lastname: Liu
authors.forename: S M
authors.initials: SM
authors.lastname: Thomas
authors.forename: D
authors.initials: D
authors.lastname: Nguyen
authors.forename: D
authors.initials: D
authors.lastname: Dudley
authors.forename: H
authors.initials: H
authors.lastname: Fraser
authors.forename: D
authors.initials: D
authors.lastname: Purich
authors.forename: M
authors.initials: M
authors.lastname: Lopez-Ilasaca
authors.forename: C
authors.initials: C
authors.lastname: Klein
authors.forename: L
authors.initials: L
authors.lastname: Davidson
authors.forename: R
authors.initials: R
authors.lastname: Bronson
authors.forename: R C
authors.initials: RC
authors.lastname: Mulligan
authors.forename: F
authors.initials: F
authors.lastname: Southwick
authors.forename: R
authors.initials: R
authors.lastname: Geha
authors.forename: M B
authors.initials: MB
authors.lastname: Goldberg
authors.forename: F S
authors.initials: FS
authors.lastname: Rosen
authors.forename: J H
authors.initials: JH
authors.lastname: Hartwig
authors.forename: F W
authors.initials: FW
authors.lastname: Alt
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000502:physiology*; D022081:Cell Surface Extensions / Q000378:metabolism*; D005314:Embryonic and Fetal Development; D005347:Fibroblasts; D018390:Gene Targeting; D008087:Listeria / Q000502:physiology; D051379:Mice; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011995:Recombination, Genetic; D012763:Shigella flexneri / Q000502:physiology; D014616:Vaccinia virus / Q000502:physiology; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal
chemical_list: D000199:Actins; D009419:Nerve Tissue Proteins; D010982:Platelet-Derived Growth Factor; C495772:Wasl protein, mouse; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal