Article abstract
Nature Cell Biology 3, 897 - 904 (2001)
Published online: 12 September 2001 | doi:10.1038/ncb1001-897
N-WASP deficiency reveals distinct pathways for cell surface projections and microbial actin-based motility
Scott B. Snapper1,2,3, Fuminao Takeshima2,3, Inés Antón4,5, Ching-Hui Liu1,2, Sheila M. Thomas3,6, Deanna Nguyen2, Darryll Dudley1, Hunter Fraser1, Daniel Purich8, Marco Lopez-Ilasaca9, Christoph Klein4,10, Laurie Davidson11, Roderick Bronson12, Richard C. Mulligan11,13, Fred Southwick8, Raif Geha4,5, Marcia B. Goldberg3,14, Fred S. Rosen1,4, John H. Hartwig7,15 & Frederick W. Alt1,11,13
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.
- Center for Blood Research, 200 Longwood Avenue, Boston, Massachusetts 02115, USA
- Gastrointestinal Unit (Medical Services) and the Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts, 02114, USA
- Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
- Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA
- Division of Immunology, Howard Hughes Medical Institute, Children's Hospital, Boston, Massachusetts 02115, USA
- Hematology Division, Beth Israel Deaconess Hospital, Boston, Massachusetts 02215, USA
- Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
- Department of Infectious Disease, University of Florida College of Medicine, Gainesville 32601, Florida, USA
- Cardiology Division, Brigham & Women's Hospital, Longwood Avenue, Boston, Massachusetts 02115, USA
- Division of Pediatric Hematology/Oncology, Howard Hughes Medical Institute, Children's Hospital, Boston, Massachusetts 02115, USA
- Howard Hughes Medical Institute, Children's Hospital, Boston, Massachusetts 02115, USA
- Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
- Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
- Infectious Disease Unit, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts, 02114, USA
- Hematology Division, Brigham & Women's Hospital, Longwood Avenue, Boston, Massachusetts 02115, USA
Correspondence to: Scott B. Snapper1,2,3 e-mail: ssnapper@hms.harvard.edu
|
MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated REFERENCE REVIEWS NEWS AND VIEWS RESEARCH |
