wiskott aldrich syndrome protein


Summary: WASP protein is mutated in WISKOTT-ALDRICH SYNDROME and is expressed primarily in hematopoietic cells. It is the founding member of the WASP protein family and interacts with CDC42 PROTEIN to help regulate ACTIN polymerization.

Top Publications

  1. Bosticardo M, Marangoni F, Aiuti A, Villa A, Grazia Roncarolo M. Recent advances in understanding the pathophysiology of Wiskott-Aldrich syndrome. Blood. 2009;113:6288-95 pubmed publisher
    ..A full understanding of these mechanisms is still needed to further implement new therapeutic strategies for this peculiar immunodeficiency. ..
  2. Fricke R, Gohl C, Dharmalingam E, Grevelhörster A, Zahedi B, Harden N, et al. Drosophila Cip4/Toca-1 integrates membrane trafficking and actin dynamics through WASP and SCAR/WAVE. Curr Biol. 2009;19:1429-37 pubmed publisher
    ..Second, Cip4 recruits WASP and WAVE proteins to induce actin polymerization, supporting vesicle scission and providing the force for vesicle movement. ..
  3. Thrasher A, Burns S. WASP: a key immunological multitasker. Nat Rev Immunol. 2010;10:182-92 pubmed publisher
    ..Here, we describe recent insights into the cellular mechanisms of these two related, but distinct, human diseases and discuss their wider implications for haematopoiesis, immune function and autoimmunity. ..
  4. Coyle I, Koh Y, Lee W, Slind J, Fergestad T, Littleton J, et al. Nervous wreck, an SH3 adaptor protein that interacts with Wsp, regulates synaptic growth in Drosophila. Neuron. 2004;41:521-34 pubmed
    ..We propose that Nwk controls synapse morphology by regulating actin dynamics downstream of growth signals in presynaptic terminals. ..
  5. Ramesh N, Geha R. Recent advances in the biology of WASP and WIP. Immunol Res. 2009;44:99-111 pubmed publisher
    ..In this review, we have summarized recent developments in the biology of WASP and the role of WIP in regulating WASP function. We also discuss WASP-independent functions of WIP. ..
  6. Yu H, Liu T, Meng W, Hou L. A novel WASP gene mutation in a Chinese boy with Wiskott-Aldrich syndrome. Int J Hematol. 2010;92:271-5 pubmed publisher
    ..Western blotting demonstrated a 28-kDa truncated WAS protein. A maternal study revealed that his mother had a heterozygous genotype, but showed normal WASP expression. ..
  7. Shi R, Liu Z, Yang Y. [WASP gene mutation analysis of a family of X-linked thrombocytopenia]. Zhongguo Dang Dai Er Ke Za Zhi. 2010;12:784-7 pubmed
    ..The patient's mother was the carrier of the heterozygosis mutation in X-chromosome. WASP mutations may be attributed to the molecular mechanism of X-linked thrombocytopenia. G291A is one of the mutations of WASP. ..
  8. Bertet C, Rauzi M, Lecuit T. Repression of Wasp by JAK/STAT signalling inhibits medial actomyosin network assembly and apical cell constriction in intercalating epithelial cells. Development. 2009;136:4199-212 pubmed publisher
    ..We discuss possible models for the role of Wasp activity in the regulation of Myo-II distribution. ..
  9. Lyubimova A, Garber J, Upadhyay G, Sharov A, Anastasoaie F, Yajnik V, et al. Neural Wiskott-Aldrich syndrome protein modulates Wnt signaling and is required for hair follicle cycling in mice. J Clin Invest. 2010;120:446-56 pubmed publisher
    ..We therefore propose that N-WASP acts as a positive regulator of beta-catenin-dependent transcription, modulating differentiation of HF progenitor cells. ..

More Information


  1. Ochs H. Mutations of the Wiskott-Aldrich Syndrome Protein affect protein expression and dictate the clinical phenotypes. Immunol Res. 2009;44:84-8 pubmed publisher
    ..However, because there are exceptions to this rule it is difficult to predict the long-term prognosis of a given affected boy solely based on the analysis of WASP expression. ..
  2. 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
  3. Gomez T, Billadeau D. A FAM21-containing WASH complex regulates retromer-dependent sorting. Dev Cell. 2009;17:699-711 pubmed publisher
  4. Rajan A, Tien A, Haueter C, Schulze K, Bellen H. The Arp2/3 complex and WASp are required for apical trafficking of Delta into microvilli during cell fate specification of sensory organ precursors. Nat Cell Biol. 2009;11:815-24 pubmed publisher
    ..Our data indicate that WASp-dependent Arp2/3 actin polymerization is crucial for apical presentation of Delta, providing a mechanistic link between actin polymerization and Notch signalling...
  5. 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
  6. Albert M, Bittner T, Nonoyama S, Notarangelo L, Burns S, Imai K, et al. X-linked thrombocytopenia (XLT) due to WAS mutations: clinical characteristics, long-term outcome, and treatment options. Blood. 2010;115:3231-8 pubmed publisher
    ..These observations will allow better decision making when considering treatment options for individual patients with XLT. ..
  7. Rajmohan R, Wong M, Meng L, Munn A, Thanabalu T. Las17p-Vrp1p but not Las17p-Arp2/3 interaction is important for actin patch polarization in yeast. Biochim Biophys Acta. 2009;1793:825-35 pubmed publisher
    ..Using these mutant and truncated forms of yeast WASP we provide novel evidence that WASP interaction with WIP is more important than interaction with Arp2/3 for polarized actin assembly and endocytosis in yeast. ..
  8. Knapek K, Frondorf K, Post J, Short S, Cox D, Gomez Cambronero J. The molecular basis of phospholipase D2-induced chemotaxis: elucidation of differential pathways in macrophages and fibroblasts. Mol Cell Biol. 2010;30:4492-506 pubmed publisher
  9. Bear J. Sorting out endosomes in the WASH. Dev Cell. 2009;17:583-4 pubmed publisher
  10. Klein I, Predescu D, Sharma T, Knezevic I, Malik A, Predescu S. Intersectin-2L regulates caveola endocytosis secondary to Cdc42-mediated actin polymerization. J Biol Chem. 2009;284:25953-61 pubmed publisher
    ..Thus, ITSN-2L, a guanine nucleotide exchange factor for Cdc42, regulates different steps of caveola endocytosis in ECs by controlling the temporal and spatial actin polymerization and remodeling sub-adjacent to the plasma membrane. ..
  11. Teitell M. Alternative control: what's WASp doing in the nucleus?. Sci Transl Med. 2010;2:37ps31 pubmed publisher
  12. Tang D, Zhang W, Gunst S. The adapter protein CrkII regulates neuronal Wiskott-Aldrich syndrome protein, actin polymerization, and tension development during contractile stimulation of smooth muscle. J Biol Chem. 2005;280:23380-9 pubmed
    ..These studies suggest a novel signaling pathway for the regulation of N-WASp activation and active contraction in smooth muscle tissues. ..
  13. Trifari S, Scaramuzza S, Catucci M, Ponzoni M, Mollica L, Chiesa R, et al. Revertant T lymphocytes in a patient with Wiskott-Aldrich syndrome: analysis of function and distribution in lymphoid organs. J Allergy Clin Immunol. 2010;125:439-448.e8 pubmed publisher
  14. Leuci V, Gammaitoni L, Capellero S, Sangiolo D, Mesuraca M, Bond H, et al. Efficient transcriptional targeting of human hematopoietic stem cells and blood cell lineages by lentiviral vectors containing the regulatory element of the Wiskott-Aldrich syndrome gene. Stem Cells. 2009;27:2815-23 pubmed publisher
    ..In particular, the 170-bp carrying vector, for its reduced size, could significantly improve the transduction/expression of large-size genes...
  15. Boztug K, Klein C. Novel genetic etiologies of severe congenital neutropenia. Curr Opin Immunol. 2009;21:472-80 pubmed publisher
    ..Despite our increasing knowledge of the genetic etiologies of SCN, the molecular pathophysiology underlying these disorders remains only partially understood. ..
  16. Zhang J, Zhang X, Guo Y, Xu L, Pei D. Sorting nexin 33 induces mammalian cell micronucleated phenotype and actin polymerization by interacting with Wiskott-Aldrich syndrome protein. J Biol Chem. 2009;284:21659-69 pubmed publisher
    ..On the other hand, knockdown of WASp alleviates the phenotype induced by SNX33. Taken together, our results suggest that SNX33 plays a role in maintaining cell shape and cell cycle progression through its interaction with WASp. ..
  17. Astrakhan A, Ochs H, Rawlings D. Wiskott-Aldrich syndrome protein is required for homeostasis and function of invariant NKT cells. J Immunol. 2009;182:7370-80 pubmed publisher
    ..Our findings highlight the crucial role for WASp in iNKT development, homeostasis, and activation, and identify iNKT dysfunction as an additional factor likely to contribute to the clinical features observed in WAS patients. ..
  18. Rangarajan E, Park H, Fortin E, Sygusch J, Izard T. Mechanism of aldolase control of sorting nexin 9 function in endocytosis. J Biol Chem. 2010;285:11983-90 pubmed publisher
  19. Gunst S, Zhang W. Actin cytoskeletal dynamics in smooth muscle: a new paradigm for the regulation of smooth muscle contraction. Am J Physiol Cell Physiol. 2008;295:C576-87 pubmed publisher
    ..Better understanding of the physiological function of these dynamic cytoskeletal processes in smooth muscle may provide important insights into the physiological regulation of smooth muscle tissues...
  20. 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
  21. De Meester J, Calvez R, Valitutti S, Dupré L. The Wiskott-Aldrich syndrome protein regulates CTL cytotoxicity and is required for efficient killing of B cell lymphoma targets. J Leukoc Biol. 2010;88:1031-40 pubmed publisher
    ..Importantly, the use of a gene therapy lentiviral vector was sufficient to restore efficient cytotoxic activity. Our study suggests that CTL dysfunction contributes to the development of hematological malignancies in WAS patients...
  22. Zencheck W, Xiao H, Nolen B, Angeletti R, Pollard T, Almo S. Nucleotide- and activator-dependent structural and dynamic changes of arp2/3 complex monitored by hydrogen/deuterium exchange and mass spectrometry. J Mol Biol. 2009;390:414-27 pubmed publisher
  23. Lee S, Han J, Leeper L, Gruver J, Chung C. Regulation of the formation and trafficking of vesicles from Golgi by PCH family proteins during chemotaxis. Biochim Biophys Acta. 2009;1793:1199-209 pubmed publisher
    ..Our results suggest that interaction of WASP with NLP/SLP is required for the formation and trafficking of vesicles from Golgi to the membrane, which might play a central role in the establishment of cell polarity during chemotaxis...
  24. Shcherbina A, Cooley J, Lutskiy M, Benarafa C, Gilbert G, REMOLD O DONNELL E. WASP plays a novel role in regulating platelet responses dependent on alphaIIbbeta3 integrin outside-in signalling. Br J Haematol. 2010;148:416-27 pubmed publisher
    ..The collective results reveal a novel function for WASP in regulating pro-aggregatory and pro-coagulant responses downstream of integrin outside-in signalling. ..
  25. Kurisu S, Takenawa T. The WASP and WAVE family proteins. Genome Biol. 2009;10:226 pubmed publisher
    ..Current efforts are focusing on integrating these pieces of molecular information to draw a unified picture of how the actin cytoskeleton in a single cell works dynamically to build multicellular organization. ..
  26. Park H, Cox D. Cdc42 regulates Fc gamma receptor-mediated phagocytosis through the activation and phosphorylation of Wiskott-Aldrich syndrome protein (WASP) and neural-WASP. Mol Biol Cell. 2009;20:4500-8 pubmed publisher
    ..These results indicate that Cdc42 is essential for the activation of WASP and N-WASP, leading to actin assembly and phagocytic cup formation by macrophages during Fc(gamma)R-mediated phagocytosis. ..
  27. Tsuboi S, Takada H, Hara T, Mochizuki N, Funyu T, Saitoh H, et al. FBP17 Mediates a Common Molecular Step in the Formation of Podosomes and Phagocytic Cups in Macrophages. J Biol Chem. 2009;284:8548-56 pubmed publisher
    ..These results provide a potential mechanism underlying the recurrent infections in WAS patients. ..
  28. Sudhaharan T, Liu P, Foo Y, Bu W, Lim K, Wohland T, et al. Determination of in vivo dissociation constant, KD, of Cdc42-effector complexes in live mammalian cells using single wavelength fluorescence cross-correlation spectroscopy. J Biol Chem. 2009;284:13602-9 pubmed publisher
    ..The determination of K(D) for Cdc42-effector interactions opens the way to describe cell signaling pathways quantitatively in vivo in mammalian cells. ..
  29. Balcer H, Daugherty Clarke K, Goode B. The p40/ARPC1 subunit of Arp2/3 complex performs multiple essential roles in WASp-regulated actin nucleation. J Biol Chem. 2010;285:8481-91 pubmed publisher
    The Arp2/3 complex is a conserved seven-subunit actin-nucleating machine activated by WASp (Wiskott Aldrich syndrome protein)...
  30. Lee W, Huang J, Jaing T, Wu K, Chien Y, Chang K. Clinical aspects and genetic analysis of taiwanese patients with wiskott-Aldrich syndrome protein mutation: the first identification of x-linked thrombocytopenia in the chinese with novel mutations. J Clin Immunol. 2010;30:593-601 pubmed publisher
  31. Qualmann B, Kessels M. New players in actin polymerization--WH2-domain-containing actin nucleators. Trends Cell Biol. 2009;19:276-85 pubmed publisher
    ..Recent studies on these WH2 proteins offer unique insight into the biological problem of actin-filament formation and how cells use specialized molecular machines to bring about so many different cytoskeletal structures. ..
  32. Crepin V, Girard F, Schüller S, Phillips A, Mousnier A, Frankel G. Dissecting the role of the Tir:Nck and Tir:IRTKS/IRSp53 signalling pathways in vivo. Mol Microbiol. 2010;75:308-23 pubmed publisher
    ..Importantly, wild-type C. rodentium out-competed the tir tyrosine mutants during mixed infections. These results uncouple the Tir:Nck and Tir:IRTKS pathways from A/E lesion formation in vivo but assign them an important in vivo role...
  33. Westerberg L, Meelu P, Baptista M, Eston M, Adamovich D, Cotta de Almeida V, et al. Activating WASP mutations associated with X-linked neutropenia result in enhanced actin polymerization, altered cytoskeletal responses, and genomic instability in lymphocytes. J Exp Med. 2010;207:1145-52 pubmed publisher
    ..These data indicate that there are unique requirements for the presence and activation status of WASP in B and T cells and that WASP-activating mutations interfere with lymphocyte cell survival and genomic stability. ..
  34. 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. ..
  35. Toscano M, Benabdellah K, Munoz P, Frecha C, Cobo M, Martin F. Was cDNA sequences modulate transgene expression of was promoter-driven lentiviral vectors. Hum Gene Ther. 2009;20:1279-90 pubmed publisher
    ..These results represent the first data showing the role of Was intragenic sequences in gene regulation. ..
  36. Le Bras S, Massaad M, Koduru S, Kumar L, Oyoshi M, Hartwig J, et al. WIP is critical for T cell responsiveness to IL-2. Proc Natl Acad Sci U S A. 2009;106:7519-24 pubmed publisher
    ..These results indicate that WIP is essential for IL-2 signaling and responsiveness in T cells, possibly because of its critical role in TCR-triggered actin cytoskeletal reorganization. ..
  37. Morales Tirado V, Sojka D, Katzman S, Lazarski C, Finkelman F, Urban J, et al. Critical requirement for the Wiskott-Aldrich syndrome protein in Th2 effector function. Blood. 2010;115:3498-507 pubmed publisher
    ..Moreover, dominant-negative WASp expression in WT effector T cells blocked IL-4 production, but had no effect on IFNgamma. Thus WASp plays a selective, posttranscriptional role in Th2 effector function...
  38. Mani M, Venkatasubrahmanyam S, Sanyal M, Levy S, Butte A, Weinberg K, et al. Wiskott-Aldrich syndrome protein is an effector of Kit signaling. Blood. 2009;114:2900-8 pubmed publisher
  39. 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. ..
  40. Liu R, Abreu Blanco M, Barry K, Linardopoulou E, Osborn G, Parkhurst S. Wash functions downstream of Rho and links linear and branched actin nucleation factors. Development. 2009;136:2849-60 pubmed publisher
    ..Our results establish Wash and Rho as regulators of both linear- and branched-actin networks, and suggest an Arp2/3-mediated mechanism for how cells might coordinately regulate these structures. ..
  41. Wong M, Meng L, Rajmohan R, Yu S, Thanabalu T. Vrp1p-Las17p interaction is critical for actin patch polarization but is not essential for growth or fluid phase endocytosis in S. cerevisiae. Biochim Biophys Acta. 2010;1803:1332-46 pubmed publisher
    ..However, Las17p-Vrp1p interaction is essential for actin patch polarization at elevated temperature. ..
  42. Rajmohan R, Raodah A, Wong M, Thanabalu T. Characterization of Wiskott-Aldrich syndrome (WAS) mutants using Saccharomyces cerevisiae. FEMS Yeast Res. 2009;9:1226-35 pubmed publisher
  43. Nikolov N, Shimizu M, Cleland S, Bailey D, Aoki J, STROM T, et al. Systemic autoimmunity and defective Fas ligand secretion in the absence of the Wiskott-Aldrich syndrome protein. Blood. 2010;116:740-7 pubmed publisher
  44. Gildor B, Massarwa R, Shilo B, Schejter E. Making muscles: Arp, two, three. Fly (Austin). 2010;4:145-8 pubmed
    ..Our approach also allows us to assess the involvement of the Arp2/3 machinery in formation of a distinct, fusion-associated actin structure. ..
  45. Mace E, Zhang J, Siminovitch K, Takei F. Elucidation of the integrin LFA-1-mediated signaling pathway of actin polarization in natural killer cells. Blood. 2010;116:1272-9 pubmed publisher
    ..This increase in PIP(2) recruits WASP to the site of LFA-1 ligation where WASP promotes Arp2/3-mediated actin polymerization. These processes are critical for the initiation of NK cell-mediated cytotoxicity...
  46. Campellone K. Cytoskeleton-modulating effectors of enteropathogenic and enterohaemorrhagic Escherichia coli: Tir, EspFU and actin pedestal assembly. FEBS J. 2010;277:2390-402 pubmed publisher
  47. Zhang Z, Xiao H, Jiang L, Zhou Y, Zhao Q, Yu J, et al. Analysis of clinical and molecular characteristics of Wiskott-Aldrich syndrome in 24 patients from 23 unrelated Chinese families. Pediatr Allergy Immunol. 2010;21:522-32 pubmed publisher
    ..WASP gene analysis can make a definite diagnosis of WAS and identify mutation carriers, beneficial for timely treatment and genetic counseling for children with WAS. ..
  48. Dovas A, Gevrey J, Grossi A, Park H, Abou Kheir W, Cox D. Regulation of podosome dynamics by WASp phosphorylation: implication in matrix degradation and chemotaxis in macrophages. J Cell Sci. 2009;122:3873-82 pubmed publisher
    ..These results suggest a more complex role for tyrosine phosphorylation than simply in the regulation of WASp activity, and suggest a link between podosome dynamics and macrophage migration. ..
  49. Marangoni F, Bosticardo M, Charrier S, Draghici E, Locci M, Scaramuzza S, et al. Evidence for long-term efficacy and safety of gene therapy for Wiskott-Aldrich syndrome in preclinical models. Mol Ther. 2009;17:1073-82 pubmed publisher
    ..Demonstration of long-term efficacy and safety of WAS gene therapy mediated by a clinically applicable LV is a key step toward the implementation of a gene therapy clinical trial for WAS. ..
  50. Burns S, Killock D, Moulding D, Metelo J, Nunes J, Taylor R, et al. A congenital activating mutant of WASp causes altered plasma membrane topography and adhesion under flow in lymphocytes. Blood. 2010;115:5355-65 pubmed publisher
    ..Together, our results demonstrate that WASp(I294T) significantly affects lymphocyte membrane topography and L-selectin-dependent adhesion, which may be linked to defective hematopoiesis and leukocyte function in affected patients. ..
  51. Cammer M, Gevrey J, Lorenz M, Dovas A, Condeelis J, Cox D. The mechanism of CSF-1-induced Wiskott-Aldrich syndrome protein activation in vivo: a role for phosphatidylinositol 3-kinase and Cdc42. J Biol Chem. 2009;284:23302-11 pubmed publisher
    ..However, although tyrosine phosphorylation of WASP has been proposed to stimulate WASP activity, we found no evidence to indicate that this occurs in vivo. ..
  52. Marathe B, Prislovsky A, Astrakhan A, Rawlings D, Wan J, Strom T. Antiplatelet antibodies in WASP(-) mice correlate with evidence of increased in vivo platelet consumption. Exp Hematol. 2009;37:1353-63 pubmed publisher
    ..Both an increased incidence of antiplatelet antibodies and an increased susceptibility to their effects contribute to antibody-dependent clearance of WASP(-) platelets. ..
  53. Davis B, Yan Q, Bui J, Felix K, Moratto D, Muul L, et al. Somatic mosaicism in the Wiskott-Aldrich syndrome: molecular and functional characterization of genotypic revertants. Clin Immunol. 2010;135:72-83 pubmed publisher