N-WASP deficiency reveals distinct pathways for cell surface projections and microbial actin-based motility.
Nat Cell Biol 2001 Oct; 3(10):897-904.
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, S B.; Takeshima, F; Anton, I; Liu, C H.; Thomas, S M.; Nguyen, D; Dudley, D; Fraser, H; Purich, D; Lopez, Ilasaca M.; Klein, C; Davidson, L; Bronson, R; Mulligan, R C.; Southwick, F; Geha, R; Goldberg, M B.; Rosen, F S.; Hartwig, J H.; and Alt, F W., " N-WASP deficiency reveals distinct pathways for cell surface projections and microbial actin-based motility." (2001). Faculty Research 2000 - 2009. 311.