Wiskott—Aldrich Syndrome: a model for defective actin reorganization, cell trafficking and synapse formation

Wiskott—Aldrich Syndrome: a model for defective actin reorganization, cell trafficking and synapse formation Review Article Pages 585-591 Luigi D Notarangelo, Hans D Ochs Close Close preview | Purchase PDF (307 K) | Related articles | Related reference work articles AbstractAbstract | Figures/TablesFigures/Tables | ReferencesReferences Abstract Wiskott–Aldrich Syndrome (WAS) is an X-linked immunodeficiency characterized by thrombocytopenia with small platelets, eczema, recurrent infections, autoimmune disorders and increased incidence of malignancies. Classic WAS, and a milder form, X-linked thrombocytopenia, are caused by mutations of the WAS protein (WASP) gene. Recent investigations have provided evidence that WASP and several related proteins are involved in the reorganization of the actin cytoskeleton by activating Arp2/3-mediated actin polymerization. This function is controlled by the small GTPase Cdc42, which regulates the autoinhibitory loop formation of WASP. In addition, WASP is involved in cytoplasmic signaling via its interaction with a variety of adaptor molecules. Mutation analysis of large cohorts of WAS/X-linked thrombocytopenia patients has provided evidence for a strong correlation between phenotype and genotype. Article Outline • Introduction • Biochemical properties and regulation of WASP • Analysis of WASP-deficient patients • Function of WASP • Consequences of WASP gene mutations • Novel therapeutic perspectives • Conclusions • References and recommended reading • Acknowledgements • References