Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Haein Park
  • Athanassios Dovas
  • Dianne CoxEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_605


Historical Background

Wiskott–Aldrich syndrome (WAS), a pediatric disorder, was first described in 1937 by Alfred Wiskott as a “hereditary thrombopathy” in males, presenting with thrombocytopenia, eczema, bloody diarrhea, episodes of fever, and recurrent bacterial infections. Robert A. Aldrich would later demonstrate an X-linked mode of inheritance of this disease. Other features of WAS were later recognized, including immunodeficiency involving both humoral and cellular immunity, high rate of autoimmunity and malignancies, abnormal apoptosis, and defective cell motility. The mutated gene giving rise to this disease was identified in 1994 by positional cloning and referred to as WAS, and mutations of the WAS protein (WASP) were demonstrated not only in patients with WAS, but also in those with X-linked thrombocytopenia (XLT), a disease showing milder clinical phenotype with a more favorable...

This is a preview of subscription content, log in to check access.


  1. Cotta-de-Almeida V, Westerberg L, Maillard MH, et al. Wiskott Aldrich syndrome protein (WASP) and N-WASP are critical for T cell development. Proc Natl Acad Sci USA. 2007;104(39):15424–9.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Dovas A, Cox D. Regulation of WASp by phosphorylation: activation or other functions? Commun Integr Biol. 2010;3(2):101–5.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Isaac BM, Ishihara D, Nusblat LM, et al. N-WASP has the ability to compensate for the loss of WASP in macrophage podosome formation and chemotaxis. Exp Cell Res. 2010;316(20):3406–16.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Lefever T, Pedersen E, Basse A, et al. N-WASP is a novel regulator of hair-follicle cycling that controls antiproliferative TGF{beta} pathways. J Cell Sci. 2010;123(Pt 1):128–40.CrossRefPubMedGoogle Scholar
  5. Miki H, Takenawa T. Regulation of actin dynamics by WASP family proteins. J Biochem. 2003;134(3):309–13.CrossRefPubMedGoogle Scholar
  6. Notarangelo LD, Miao CH, Ochs HD. Wiskott-Aldrich syndrome. Curr Opin Hematol. 2008;15(1):30–6.CrossRefPubMedGoogle Scholar
  7. Novak N, Bar V, Sabanay H, et al. N-WASP is required for membrane wrapping and myelination by Schwann cells. J Cell Biol. 2011;192(2):243–50.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Nusblat LM, Dovas A, Cox D. The non-redundant role of N-WASP in podosome-mediated matrix degradation in macrophages. Eur J Cell Biol. 2011;90(2–3):205–12.CrossRefPubMedGoogle Scholar
  9. Padrick SB, Rosen MK. Physical mechanisms of signal integration by WASP family proteins. Annu Rev Biochem. 2010;79:707–35.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 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(21):4500–8.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Ramesh N, Geha R. Recent advances in the biology of WASP and WIP. Immunol Res. 2009;44(1–3):99–111.CrossRefPubMedGoogle Scholar
  12. Snapper SB, Takeshima F, Anton I, et al. N-WASP deficiency reveals distinct pathways for cell surface projections and microbial actin-based motility. Nat Cell Biol. 2001;3(10):897–904.CrossRefPubMedGoogle Scholar
  13. Takano K, Watanabe-Takano H, Suetsugu S, et al. Nebulin and N-WASP cooperate to cause IGF-1-induced sarcomeric actin filament formation. Science. 2010;330(6010):1536–40.CrossRefPubMedGoogle Scholar
  14. Takenawa T, Suetsugu S. The WASP-WAVE protein network: connecting the membrane to the cytoskeleton. Nat Rev Mol Cell Biol. 2007;8(1):37–48.CrossRefPubMedGoogle Scholar
  15. Taylor MD, Sadhukhan S, Kottangada P, et al. Nuclear role of WASp in the pathogenesis of dysregulated TH1 immunity in human Wiskott-Aldrich syndrome. Sci Transl Med. 2010;2(37):37–44.CrossRefGoogle Scholar
  16. Thrasher AJ, Burns SO. WASP: a key immunological multitasker. Nat Rev Immunol. 2010;10(3):182–92.CrossRefPubMedGoogle Scholar
  17. Tomasevic N, Jia Z, Russell A, et al. Differential regulation of WASP and N-WASP by Cdc42, Rac1, Nck, and PI(4,5)P2. Biochemistry. 2007;46(11):3494–502.CrossRefPubMedGoogle Scholar
  18. Veltman DM, Insall RH. WASP family proteins: their evolution and its physiological implications. Mol Biol Cell. 2010;21(16):2880–93.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Wu X, Yoo Y, Okuhama NN, et al. Regulation of RNA-polymerase-II-dependent transcription by N-WASP and its nuclear-binding partners. Nat Cell Biol. 2006;8(7):756–63.CrossRefPubMedGoogle Scholar
  20. Zalevsky J, Lempert L, Kranitz H, et al. Different WASP family proteins stimulate different Arp2/3 complex-dependent actin-nucleating activities. Curr Biol. 2001;11(24):1903–13.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Anatomy and Structural BiologyAlbert Einstein College of Medicine, Jack and Pearl Resnick CampusBronxUSA