Wiskott-Aldrich syndrome protein, WASP

Wiskott-Aldrich Syndrome protein (WASP) is the product of the gene mutated in children with Wiskott-Aldrich Syndrome (WAS). It is a predominantly cyto plasmic protein, expressed only in haematopoietic cells. It binds in vivo t o the adaptor proteins Nck and Grb2, to the cytoplasmic protein-tyrosine ki nase Fyn and to the small Rho-like GTPase Cdc42, which is required for form ation of filopodia in fibroblasts and macrophages. WASP also interacts, dir ectly or indirectly, with the actin cytoskeleton. Together with studies of a closely related, ubiquitously expressed protein named N-WASP, these findi ngs suggest that WASP is a component of signalling pathways that control re organisation of the actin cytoskeleton in haematopoietic cells in response to external stimuli. In support of this idea, haematopoietic cells from WAS patients show defects in cytoskeletal organisation that compromise their a bility to polarise and to migrate in response to physiological stimuli. The se defects could account for many of the clinical features of WAS. WAS is n ow a candidate for gene therapy based on the delivery of a wild-type WASP g ene to autologous haematopoietic stem cells. In addition, recent studies of cell defects in WAS patients suggest that it may prove possible, in time, to rescue WAS cells using more conventional drug therapies. (C) 1999 Elsevi er Science Ltd. All rights reserved.