wiskott aldrich syndrome protein family


Summary: A family of microfilament proteins whose name derives from the fact that mutations in members of this protein family have been associated with WISKOTT-ALDRICH SYNDROME. They are involved in ACTIN polymerization and contain a polyproline-rich region that binds to PROFILIN, and a verprolin homology domain that binds G-ACTIN.

Top Publications

  1. Ismail A, Padrick S, Chen B, Umetani J, Rosen M. The WAVE regulatory complex is inhibited. Nat Struct Mol Biol. 2009;16:561-3 pubmed publisher
    ..Our observations identify core components needed for WAVE inhibition, reconcile contradictory existing mechanisms and reveal common regulatory principles for the WAVE/WASP family of proteins. ..
  2. Padrick S, Rosen M. Physical mechanisms of signal integration by WASP family proteins. Annu Rev Biochem. 2010;79:707-35 pubmed publisher
    ..These regulatory principles, derived from studies of WASP and N-WASP, are likely to apply broadly across the family...
  3. Jia D, Gomez T, Metlagel Z, Umetani J, Otwinowski Z, Rosen M, et al. WASH and WAVE actin regulators of the Wiskott-Aldrich syndrome protein (WASP) family are controlled by analogous structurally related complexes. Proc Natl Acad Sci U S A. 2010;107:10442-7 pubmed publisher
    ..Strumpellin is mutated in the human disease hereditary spastic paraplegia, and its link to WASH suggests that misregulation of actin dynamics on endosomes may play a role in this disorder. ..
  4. Campellone K, Welch M. A nucleator arms race: cellular control of actin assembly. Nat Rev Mol Cell Biol. 2010;11:237-51 pubmed publisher
    ..Formin nucleators with additional biochemical and cellular activities have also been uncovered. Finally, the Spire, cordon-bleu and leiomodin nucleators have revealed new ways of overcoming the kinetic barriers to actin polymerization. ..
  5. Lebensohn A, Kirschner M. Activation of the WAVE complex by coincident signals controls actin assembly. Mol Cell. 2009;36:512-24 pubmed publisher
    ..These results explain how the WAVE complex can integrate coincident signals to promote localized actin nucleation during cell motility. ..
  6. Boztug K, Schmidt M, Schwarzer A, Banerjee P, Díez I, Dewey R, et al. Stem-cell gene therapy for the Wiskott-Aldrich syndrome. N Engl J Med. 2010;363:1918-27 pubmed publisher
    ..Funded by Deutsche Forschungsgemeinschaft and others; German Clinical Trials Register number, DRKS00000330.). ..
  7. Takahashi K, Suzuki K. WAVE2 targeting to phosphatidylinositol 3,4,5-triphosphate mediated by insulin receptor substrate p53 through a complex with WAVE2. Cell Signal. 2010;22:1708-16 pubmed publisher
  8. Ducka A, Joel P, Popowicz G, Trybus K, Schleicher M, Noegel A, et al. Structures of actin-bound Wiskott-Aldrich syndrome protein homology 2 (WH2) domains of Spire and the implication for filament nucleation. Proc Natl Acad Sci U S A. 2010;107:11757-62 pubmed publisher
    ..These Spire structures are distant from those seen in the filamentous nuclei of Arp2/3, formins, and in the F-actin filament. ..
  9. Roignot J, Taieb D, Suliman M, Dusetti N, Iovanna J, Soubeyran P. CIP4 is a new ArgBP2 interacting protein that modulates the ArgBP2 mediated control of WAVE1 phosphorylation and cancer cell migration. Cancer Lett. 2010;288:116-23 pubmed publisher
    ..Finally, we could show that CIP4 was dispensable for the ArgBP2 induced blockade of cell migration whereas its overexpression was deleterious for this important function of ArgBP2. ..

More Information


  1. Derivery E, Lombard B, Loew D, Gautreau A. The Wave complex is intrinsically inactive. Cell Motil Cytoskeleton. 2009;66:777-90 pubmed publisher
    ..Importantly, the approach we describe here for multiprotein complex purification is likely applicable to a wide range of human multiprotein complexes. ..
  2. Kang H, Wang J, Longley S, Tang J, Shaw S. Relative actin nucleation promotion efficiency by WASP and WAVE proteins in endothelial cells. Biochem Biophys Res Commun. 2010;400:661-6 pubmed publisher
  3. Eriksson T, Varshney G, Aspenstrom P, Palmer R. Characterisation of the role of Vrp1 in cell fusion during the development of visceral muscle of Drosophila melanogaster. BMC Dev Biol. 2010;10:86 pubmed publisher
  4. Harmon B, Campbell N, Ratner L. Role of Abl kinase and the Wave2 signaling complex in HIV-1 entry at a post-hemifusion step. PLoS Pathog. 2010;6:e1000956 pubmed publisher
    ..These results suggest a potential utility of Abl kinase inhibitors to treat HIV-1 infected patients...
  5. Derivery E, Gautreau A. Generation of branched actin networks: assembly and regulation of the N-WASP and WAVE molecular machines. Bioessays. 2010;32:119-31 pubmed publisher
    ..Moreover, this review attempts to put together diverse observations concerning the WAVE complex in the conceptual frame of an in vivo assembly pathway that has gained support from the recent identification of a precursor. ..
  6. Zhang J, Dong B, Siminovitch K. Contributions of Wiskott-Aldrich syndrome family cytoskeletal regulatory adapters to immune regulation. Immunol Rev. 2009;232:175-94 pubmed publisher
  7. Sossey Alaoui K, Bialkowska K, Plow E. The miR200 family of microRNAs regulates WAVE3-dependent cancer cell invasion. J Biol Chem. 2009;284:33019-29 pubmed publisher
    ..In conclusion, a novel mechanism for the regulation of WAVE3 expression in cancer cells has been identified, which controls the invasive properties and morphology of cancer cells associated with their metastatic potential. ..
  8. Sanz Moreno V, Marshall C. Rho-GTPase signaling drives melanoma cell plasticity. Cell Cycle. 2009;8:1484-7 pubmed
    ..We identified two important signaling pathways regulating amoeboid and mesenchymal types of motility in melanoma. Here, we discuss our findings in the context of how specificity of Rho signaling is achieved by GEFs and GAPs. ..
  9. Takata K, Kitamura Y, Nakata Y, Matsuoka Y, Tomimoto H, Taniguchi T, et al. Involvement of WAVE accumulation in Abeta/APP pathology-dependent tangle modification in Alzheimer's disease. Am J Pathol. 2009;175:17-24 pubmed publisher
  10. Chen Z, Borek D, Padrick S, Gomez T, Metlagel Z, Ismail A, et al. Structure and control of the actin regulatory WAVE complex. Nature. 2010;468:533-8 pubmed publisher
    ..The spatial proximity of the Rac binding site and the large basic surface of the WRC suggests how the GTPase and phospholipids could cooperatively recruit the complex to membranes. ..
  11. Kelly A, Kranitz H, Dötsch V, Mullins R. Actin binding to the central domain of WASP/Scar proteins plays a critical role in the activation of the Arp2/3 complex. J Biol Chem. 2006;281:10589-97 pubmed
  12. Yang J, Li J, Wang J, Zhang C. Molecular modeling of BAD complex resided in a mitochondrion integrating glycolysis and apoptosis. J Theor Biol. 2010;266:231-41 pubmed publisher
    ..This is helpful for our development and research of the molecular mechanism of BAD integrating glycolysis and apoptosis. ..
  13. Fumoto S, Nishi J, Ishii H, Wang X, Miyamoto H, Yoshikawa N, et al. Rac-mediated macropinocytosis is a critical route for naked plasmid DNA transfer in mice. Mol Pharm. 2009;6:1170-9 pubmed publisher
    ..Overall, it was demonstrated that the Rac signaling pathway regulated the macropinocytosis of naked pDNA. The information in this study would be helpful to clarify in vivo cell functions and to improve in vivo transfection efficiency. ..
  14. Groves J, Kuriyan J. Molecular mechanisms in signal transduction at the membrane. Nat Struct Mol Biol. 2010;17:659-65 pubmed publisher
  15. Brooks S, Coccia M, Tang H, Kanuga N, Machesky L, Bailly M, et al. The Nance-Horan syndrome protein encodes a functional WAVE homology domain (WHD) and is important for co-ordinating actin remodelling and maintaining cell morphology. Hum Mol Genet. 2010;19:2421-32 pubmed publisher
    ..Our data identify NHS as a new regulator of actin remodelling. We suggest that NHS orchestrates actin regulatory protein function in response to signalling events during development. ..
  16. Pan Y, Viklund I, Tsai H, Pettersson S, Maruyama I. The ulcerative colitis marker protein WAFL interacts with accessory proteins in endocytosis. Int J Biol Sci. 2010;6:163-71 pubmed
    ..Therefore, these results suggest that WAFL may play an important role in endocytosis and subsequent membrane trafficking by interacting with AP2 through KIAA0196 and KIAA1033. ..
  17. Morimura S, Suzuki K, Takahashi K. BetaPIX and GIT1 regulate HGF-induced lamellipodia formation and WAVE2 transport. Biochem Biophys Res Commun. 2009;382:614-9 pubmed publisher
    ..Collectively, we suggest that betaPIX releases cells from the GIT1-mediated suppression of HGF-independent responses and recruits GIT1 to WAVE2, thereby facilitating HGF-induced WAVE2 transport and lamellipodia formation. ..
  18. Borth N, Walther A, Reijnst P, Jorde S, Schaub Y, Wendland J. Candida albicans Vrp1 is required for polarized morphogenesis and interacts with Wal1 and Myo5. Microbiology. 2010;156:2962-9 pubmed publisher
    ..This suggests that a Wal1-Vrp1-Myo5 complex plays an important role in endocytosis and the polarized localization of the cortical actin cytoskeleton to promote polarized hyphal growth in C. albicans...
  19. Fernando H, Sanders A, Kynaston H, Jiang W. WAVE3 is associated with invasiveness in prostate cancer cells. Urol Oncol. 2010;28:320-7 pubmed publisher
    ..This study shows that WAVE3 is pivotal in controlling the invasiveness of prostate cancer cells. Further work is needed to assess WAVE3 as a potential marker for predicting tumor aggressiveness. ..
  20. Ogaeri T, Eto K, Otsu M, Ema H, Nakauchi H. The actin polymerization regulator WAVE2 is required for early bone marrow repopulation by hematopoietic stem cells. Stem Cells. 2009;27:1120-9 pubmed publisher
  21. Kang R, Tang D, Yu Y, Wang Z, Hu T, Wang H, et al. WAVE1 regulates Bcl-2 localization and phosphorylation in leukemia cells. Leukemia. 2010;24:177-86 pubmed publisher
    ..Taken together, these results suggest WAVE1 as a novel regulator of apoptosis, and potential drug target for therapeutic intervention of leukemia. ..
  22. Takahashi K, Tanaka T, Suzuki K. Directional control of WAVE2 membrane targeting by EB1 and phosphatidylinositol 3,4,5-triphosphate. Cell Signal. 2010;22:510-8 pubmed publisher
  23. Kurisu S, Takenawa T. WASP and WAVE family proteins: friends or foes in cancer invasion?. Cancer Sci. 2010;101:2093-104 pubmed publisher
  24. Sanchez A, Flamini M, Fu X, Mannella P, Giretti M, Goglia L, et al. Rapid signaling of estrogen to WAVE1 and moesin controls neuronal spine formation via the actin cytoskeleton. Mol Endocrinol. 2009;23:1193-202 pubmed publisher
  25. Bulgin R, Arbeloa A, Goulding D, Dougan G, Crepin V, Raymond B, et al. The T3SS effector EspT defines a new category of invasive enteropathogenic E. coli (EPEC) which form intracellular actin pedestals. PLoS Pathog. 2009;5:e1000683 pubmed publisher
    ..Moreover, our data breaks the dogma of EPEC as an extracellular pathogen and defines a new category of invasive EPEC. ..
  26. Ceglia I, Kim Y, Nairn A, Greengard P. Signaling pathways controlling the phosphorylation state of WAVE1, a regulator of actin polymerization. J Neurochem. 2010;114:182-90 pubmed publisher
    ..These phosphatases act on different sites to mediate receptor-induced signaling pathways, which would lead to activation of WAVE1. ..
  27. Namekata K, Harada C, Taya C, Guo X, Kimura H, Parada L, et al. Dock3 induces axonal outgrowth by stimulating membrane recruitment of the WAVE complex. Proc Natl Acad Sci U S A. 2010;107:7586-91 pubmed publisher
    ..Our results highlight a unique mechanism through which Dock-GEFs achieve spatial and temporal restriction of WAVE signaling, and identify Dock-GEF activity as a potential therapeutic target for axonal regeneration. ..
  28. Eiseler T, Hausser A, De Kimpe L, Van Lint J, Pfizenmaier K. Protein kinase D controls actin polymerization and cell motility through phosphorylation of cortactin. J Biol Chem. 2010;285:18672-83 pubmed publisher
    ..Accordingly, cortactin-S298A significantly enhanced lamellipodia extension and directed cell migration. Our data thus unravel a previously unrecognized mechanism by which PKD controls cancer cell motility. ..
  29. Husson C, Cantrelle F, Roblin P, Didry D, Le K, Perez J, et al. Multifunctionality of the beta-thymosin/WH2 module: G-actin sequestration, actin filament growth, nucleation, and severing. Ann N Y Acad Sci. 2010;1194:44-52 pubmed publisher
    ..Novel regulation pathways in actin assembly emerge from these additional activities. ..
  30. Boettner D, D Agostino J, Torres O, Daugherty Clarke K, Uygur A, Reider A, et al. The F-BAR protein Syp1 negatively regulates WASp-Arp2/3 complex activity during endocytic patch formation. Curr Biol. 2009;19:1979-87 pubmed publisher
    ..Together, these data identify Syp1 as a novel negative regulator of WASp-Arp2/3 complex that helps choreograph the precise timing of actin assembly during endocytosis. ..
  31. Robens J, Yeow Fong L, Ng E, Hall C, Manser E. Regulation of IRSp53-dependent filopodial dynamics by antagonism between 14-3-3 binding and SH3-mediated localization. Mol Cell Biol. 2010;30:829-44 pubmed publisher
  32. Cai X, Xiao T, James S, Da J, Lin D, Liu Y, et al. Metastatic potential of lung squamous cell carcinoma associated with HSPC300 through its interaction with WAVE2. Lung Cancer. 2009;65:299-305 pubmed publisher
    ..7% of primary tumours with lymph node metastases. We hypothesize that HSPC300 is associated with metastatic potential of lung squamous cell carcinoma through its interaction with WAVE2. ..
  33. Tahirovic S, Hellal F, Neukirchen D, Hindges R, Garvalov B, FLYNN K, et al. Rac1 regulates neuronal polarization through the WAVE complex. J Neurosci. 2010;30:6930-43 pubmed publisher
    ..In addition, pharmacological inhibition of the WAVE complex effector Arp2/3 also reduced axon growth. We propose that Rac1 recruits the WAVE complex to the plasma membrane to enable actin remodeling necessary for axon growth. ..
  34. Teng Y, Ren M, Cheney R, Sharma S, Cowell J. Inactivation of the WASF3 gene in prostate cancer cells leads to suppression of tumorigenicity and metastases. Br J Cancer. 2010;103:1066-75 pubmed publisher
    ..Overall, these observations demonstrate a critical role for WASF3 in the progression of prostate cancer and identify a potential target to control tumorigenicity and metastasis. ..
  35. Rhomberg T, Truttmann M, Guye P, Ellner Y, Dehio C. A translocated protein of Bartonella henselae interferes with endocytic uptake of individual bacteria and triggers uptake of large bacterial aggregates via the invasome. Cell Microbiol. 2009;11:927-45 pubmed publisher