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Gene Review

Wasl  -  Wiskott-Aldrich syndrome-like (human)

Mus musculus

Synonyms: 2900021I12Rik, 3110031I02Rik, N-WASP, Neural Wiskott-Aldrich syndrome protein
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Disease relevance of Wasl

  • Our results indicate that WIP and N-WASP may act as a functional unit in filopodium formation, which is consistent with their role in actin-tail formation in cells infected with vaccinia virus or Shigella [1].
  • In addition, enteropathogenic Escherichia coli were incapable of inducing the formation of actin pedestals in N-WASP-defective cells [2].

High impact information on Wasl


Biological context of Wasl

  • We suggest that N-WASP and the Arp2/3 complex trigger actin polymerization during a late step in clathrin-mediated endocytosis, and propel clathrin-coated pits or vesicles from the plasma membrane into the cytoplasm [4].
  • Together, these results suggest a novel regulatory mechanism of N-WASP by tyrosine phosphorylation and subcellular localization and its potential role in the regulation of cell migration [5].
  • 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 [6].
  • Whereas N-WASP-deficient embryos survive beyond gastrulation and initiate organogenesis, they have marked developmental delay and die before embryonic day 12 [6].
  • Twinfilin replaces capping protein and promotes motility of N-WASP functionalized beads in a biomimetic motility assay, indicating that the capping activity supports twinfilin's function in motility [7].

Anatomical context of Wasl


Associations of Wasl with chemical compounds

  • In contrast, wiskostatin, a chemical inhibitor of N-WASP, potently suppressed dorsal ruffle formation in a dose-dependent manner [10].

Physical interactions of Wasl

  • Here we show that WASP-interacting protein (WIP) interacts directly with N-WASP and actin [1].
  • We first isolated N-WASP as one of the proteins bound to Ash/Grb2 SH3 domain [11].
  • In addition, this actin-clustering could not be suppressed by the coexpression of the Arp2/3 complex-sequestering fragment (CA-region) derived from N-WASP, which clearly inhibits Rac-induced membrane ruffling [12].

Regulatory relationships of Wasl

  • N-WASP activates Arp2/3 complex-dependent actin polymerization through the VCA region, leading to filopodium formation [11].

Other interactions of Wasl


Analytical, diagnostic and therapeutic context of Wasl

  • We employed Cre/loxP-mediated gene targeting to disrupt the ubiquitously expressed N-WASP in the mouse germline, which led to embryonic lethality [2].
  • A partial reversal of the T-cell signaling defect could also be achieved following transplantation of WASP-deficient HSCs expressing the WASP-homologous protein N-WASP [15].


  1. WIP regulates N-WASP-mediated actin polymerization and filopodium formation. Martinez-Quiles, N., Rohatgi, R., Antón, I.M., Medina, M., Saville, S.P., Miki, H., Yamaguchi, H., Takenawa, T., Hartwig, J.H., Geha, R.S., Ramesh, N. Nat. Cell Biol. (2001) [Pubmed]
  2. Actin pedestal formation by enteropathogenic Escherichia coli and intracellular motility of Shigella flexneri are abolished in N-WASP-defective cells. Lommel, S., Benesch, S., Rottner, K., Franz, T., Wehland, J., Kühn, R. EMBO Rep. (2001) [Pubmed]
  3. EphB receptors regulate dendritic spine development via intersectin, Cdc42 and N-WASP. Irie, F., Yamaguchi, Y. Nat. Neurosci. (2002) [Pubmed]
  4. Neural Wiskott Aldrich Syndrome Protein (N-WASP) and the Arp2/3 complex are recruited to sites of clathrin-mediated endocytosis in cultured fibroblasts. Merrifield, C.J., Qualmann, B., Kessels, M.M., Almers, W. Eur. J. Cell Biol. (2004) [Pubmed]
  5. Focal adhesion kinase regulation of N-WASP subcellular localization and function. Wu, X., Suetsugu, S., Cooper, L.A., Takenawa, T., Guan, J.L. J. Biol. Chem. (2004) [Pubmed]
  6. N-WASP deficiency reveals distinct pathways for cell surface projections and microbial actin-based motility. Snapper, S.B., Takeshima, F., Antón, 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., Alt, F.W. Nat. Cell Biol. (2001) [Pubmed]
  7. Mammalian twinfilin sequesters ADP-G-actin and caps filament barbed ends: implications in motility. Helfer, E., Nevalainen, E.M., Naumanen, P., Romero, S., Didry, D., Pantaloni, D., Lappalainen, P., Carlier, M.F. EMBO J. (2006) [Pubmed]
  8. Intersectin 1L guanine nucleotide exchange activity is regulated by adjacent src homology 3 domains that are also involved in endocytosis. Zamanian, J.L., Kelly, R.B. Mol. Biol. Cell (2003) [Pubmed]
  9. Sustained activation of N-WASP through phosphorylation is essential for neurite extension. Suetsugu, S., Hattori, M., Miki, H., Tezuka, T., Yamamoto, T., Mikoshiba, K., Takenawa, T. Dev. Cell (2002) [Pubmed]
  10. N-wasp involvement in dorsal ruffle formation in mouse embryonic fibroblasts. Legg, J.A., Bompard, G., Dawson, J., Morris, H.L., Andrew, N., Cooper, L., Johnston, S.A., Tramountanis, G., Machesky, L.M. Mol. Biol. Cell (2007) [Pubmed]
  11. From N-WASP to WAVE: key molecules for regulation of cortical actin organization. Takenawa, T. Novartis Found. Symp. (2005) [Pubmed]
  12. Arp2/3 complex-independent actin regulatory function of WAVE. Sasaki, N., Miki, H., Takenawa, T. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  13. N-WASP and WAVE2 acting downstream of phosphatidylinositol 3-kinase are required for myogenic cell migration induced by hepatocyte growth factor. Kawamura, K., Takano, K., Suetsugu, S., Kurisu, S., Yamazaki, D., Miki, H., Takenawa, T., Endo, T. J. Biol. Chem. (2004) [Pubmed]
  14. Involvement of the Arp2/3 complex and Scar2 in Golgi polarity in scratch wound models. Magdalena, J., Millard, T.H., Etienne-Manneville, S., Launay, S., Warwick, H.K., Machesky, L.M. Mol. Biol. Cell (2003) [Pubmed]
  15. Gene therapy for Wiskott-Aldrich syndrome: rescue of T-cell signaling and amelioration of colitis upon transplantation of retrovirally transduced hematopoietic stem cells in mice. Klein, C., Nguyen, D., Liu, C.H., Mizoguchi, A., Bhan, A.K., Miki, H., Takenawa, T., Rosen, F.S., Alt, F.W., Mulligan, R.C., Snapper, S.B. Blood (2003) [Pubmed]
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