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.