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.
Snapper
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SB
Center for Blood Research, 200 Longwood Avenue, Boston, Massachusetts 02115, USA. ssnapper@hms.harvard.edu
Takeshima
F
F
Antón
I
I
Liu
C H
CH
Thomas
S M
SM
Nguyen
D
D
Dudley
D
D
Fraser
H
H
Purich
D
D
Lopez-Ilasaca
M
M
Klein
C
C
Davidson
L
L
Bronson
R
R
Mulligan
R C
RC
Southwick
F
F
Geha
R
R
Goldberg
M B
MB
Rosen
F S
FS
Hartwig
J H
JH
Alt
F W
FW
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
D000199:Actins; D009419:Nerve Tissue Proteins; D010982:Platelet-Derived Growth Factor; C495772:Wasl protein, mouse; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal