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Gene Review

Wasf1  -  WAS protein family, member 1

Mus musculus

Synonyms: AI195380, AI838537, Protein WAVE-1, Scar, WASP family protein member 1, ...
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Disease relevance of Wasf1

  • Scar/WAVE-1, a Wiskott-Aldrich syndrome protein, assembles an actin-associated multi-kinase scaffold [1].
  • Malignant B16F10 mouse melanoma cells expressed more WAVE1 and WAVE2 proteins and showed higher Rac activity than B16 parental cells, which are neither invasive nor metastatic [2].

Psychiatry related information on Wasf1

  • These sensorimotor and cognitive deficits are analogous to the symptoms of patients with 3p-syndrome mental retardation who are haploinsufficient for WRP/MEGAP, a component of the WAVE-1 signaling network [3].

High impact information on Wasf1

  • Immunocytochemical analyses in Swiss 3T3 fibroblasts suggest that the WAVE-1 kinase scaffold is assembled dynamically as WAVE, PKA and Abl translocate to sites of actin reorganization in response to platelet-derived growth factor treatment [1].
  • The Scar/WAVE family of scaffolding proteins organize molecular networks that relay signals from the GTPase Rac to the actin cytoskeleton [3].
  • The WAVE-1 isoform is a brain-specific protein expressed in variety of areas including the regions of the hippocampus and the Purkinje cells of the cerebellum [3].
  • Although the VCA domain imbues WASp and other WASp family members with the capacity to modulate cytoskeletal organization, little is known about the impact of this domain activity on lymphoid cell function [4].
  • Thus, Abi-1 undergoes nucleocytoplasmic shuttling and functions at the leading edge to regulate Wave-1 localization and protein levels [5].

Biological context of Wasf1


Anatomical context of Wasf1


Associations of Wasf1 with chemical compounds

  • The mouse Wave1 complementary DNA encodes a predicted 559 amino acid protein, with a SCAR homology domain, a basic domain, a proline-rich region, a WASP homology domain and an acidic domain conserved in the orthologous proteins [8].
  • The localisation of Scar was facilitated by the finding that the formerly described inhibition of lamellipodia formation by ectopical expression of Scar, could be overcome by the treatment of cells with aluminium fluoride [13].
  • In the pretest nimodipine significantly increased the latency of Wave P1 of the ABR (mean difference: 0.16 ms; P < 0.02), showing that calcium blockade depressed sensorineural efficiency, but ABR thresholds were not affected [14].
  • Difficulty in growing cholesterol-dependent NS0 cells in the Wave bioreactor using the original low-density polypropylene (LDPE) bags has been encountered [15].
  • Cyclic AMP (cAMP) signalling reduces phosphorylation of the Cdk5 sites in WAVE1, and increases spine density in a WAVE1-dependent manner [16].

Enzymatic interactions of Wasf1


Other interactions of Wasf1

  • The effect of WAVE2 silencing by RNA interference (RNAi) on the highly invasive nature of B16F10 cells was more dramatic than that of WAVE1 RNAi [2].
  • Gene targeting experiments in mice demonstrate that WRP anchoring to WAVE-1 is a homeostatic mechanism that contributes to neuronal development and the fidelity of synaptic connectivity [17].
  • Next, we found WAVE1, WAVE2 and WAVE3 [18].
  • WAVE1 has been reported to associate and activate Arp2/3 complex at its C-terminal region that is rich in acidic residues [19].
  • Phosphorylation of WAVE1 by Cdk5 inhibits its ability to regulate Arp2/3 complex-dependent actin polymerization [16].


  1. Scar/WAVE-1, a Wiskott-Aldrich syndrome protein, assembles an actin-associated multi-kinase scaffold. Westphal, R.S., Soderling, S.H., Alto, N.M., Langeberg, L.K., Scott, J.D. EMBO J. (2000) [Pubmed]
  2. Rac-WAVE2 signaling is involved in the invasive and metastatic phenotypes of murine melanoma cells. Kurisu, S., Suetsugu, S., Yamazaki, D., Yamaguchi, H., Takenawa, T. Oncogene (2005) [Pubmed]
  3. Loss of WAVE-1 causes sensorimotor retardation and reduced learning and memory in mice. Soderling, S.H., Langeberg, L.K., Soderling, J.A., Davee, S.M., Simerly, R., Raber, J., Scott, J.D. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  4. WASp verprolin homology, cofilin homology, and acidic region domain-mediated actin polymerization is required for T cell development. Zhang, J., Shi, F., Badour, K., Deng, Y., McGavin, M.K., Siminovitch, K.A. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  5. Abl interactor 1 (Abi-1) wave-binding and SNARE domains regulate its nucleocytoplasmic shuttling, lamellipodium localization, and wave-1 levels. Echarri, A., Lai, M.J., Robinson, M.R., Pendergast, A.M. Mol. Cell. Biol. (2004) [Pubmed]
  6. Genomic organization and expression profile of the human and mouse WAVE gene family. Sossey-Alaoui, K., Head, K., Nowak, N., Cowell, J.K. Mamm. Genome (2003) [Pubmed]
  7. ABI2-deficient mice exhibit defective cell migration, aberrant dendritic spine morphogenesis, and deficits in learning and memory. Grove, M., Demyanenko, G., Echarri, A., Zipfel, P.A., Quiroz, M.E., Rodriguiz, R.M., Playford, M., Martensen, S.A., Robinson, M.R., Wetsel, W.C., Maness, P.F., Pendergast, A.M. Mol. Cell. Biol. (2004) [Pubmed]
  8. Characterization and expression analyses of the mouse Wiskott-Aldrich syndrome protein (WASP) family member Wave1/Scar. Benachenhou, N., Massy, I., Vacher, J. Gene (2002) [Pubmed]
  9. Characterization of the WAVE1 knock-out mouse: implications for CNS development. Dahl, J.P., Wang-Dunlop, J., Gonzales, C., Goad, M.E., Mark, R.J., Kwak, S.P. J. Neurosci. (2003) [Pubmed]
  10. Normal Arp2/3 complex activation in platelets lacking WASp. Falet, H., Hoffmeister, K.M., Neujahr, R., Hartwig, J.H. Blood (2002) [Pubmed]
  11. A novel function of WAVE in lamellipodia: WAVE1 is required for stabilization of lamellipodial protrusions during cell spreading. Yamazaki, D., Fujiwara, T., Suetsugu, S., Takenawa, T. Genes Cells (2005) [Pubmed]
  12. Role for the Abi/wave protein complex in T cell receptor-mediated proliferation and cytoskeletal remodeling. Zipfel, P.A., Bunnell, S.C., Witherow, D.S., Gu, J.J., Chislock, E.M., Ring, C., Pendergast, A.M. Curr. Biol. (2006) [Pubmed]
  13. Scar/WAVE is localised at the tips of protruding lamellipodia in living cells. Hahne, P., Sechi, A., Benesch, S., Small, J.V. FEBS Lett. (2001) [Pubmed]
  14. Nimodipine at a dose that slows ABR latencies does not protect the ear against noise. Ison, J.R., Payman, G.H., Palmer, M.J., Walton, J.P. Hear. Res. (1997) [Pubmed]
  15. Growing cholesterol-dependent NS0 myeloma cell line in the wave bioreactor system: overcoming cholesterol-polymer interaction by using pretreated polymer or inert fluorinated ethylene propylene. Kadarusman, J., Bhatia, R., McLaughlin, J., Lin, W.R. Biotechnol. Prog. (2005) [Pubmed]
  16. Phosphorylation of WAVE1 regulates actin polymerization and dendritic spine morphology. Kim, Y., Sung, J.Y., Ceglia, I., Lee, K.W., Ahn, J.H., Halford, J.M., Kim, A.M., Kwak, S.P., Park, J.B., Ho Ryu, S., Schenck, A., Bardoni, B., Scott, J.D., Nairn, A.C., Greengard, P. Nature (2006) [Pubmed]
  17. A WAVE-1 and WRP signaling complex regulates spine density, synaptic plasticity, and memory. Soderling, S.H., Guire, E.S., Kaech, S., White, J., Zhang, F., Schutz, K., Langeberg, L.K., Banker, G., Raber, J., Scott, J.D. J. Neurosci. (2007) [Pubmed]
  18. From N-WASP to WAVE: key molecules for regulation of cortical actin organization. Takenawa, T. Novartis Found. Symp. (2005) [Pubmed]
  19. Arp2/3 complex-independent actin regulatory function of WAVE. Sasaki, N., Miki, H., Takenawa, T. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
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