The Wiskott–Aldrich syndrome

The biological mechanisms responsible for the pathophysiology of the Wiskott–Aldrich syndrome (WAS) have been shown to be linked to the regulation of actin polymerization in haematopoietic cells. WAS protein (WASp) is now known to be a member of a unique family sharing similar domain structures, which are responsible for transduction of signals from the cell membrane to the actin cytoskeleton. The interaction between WASp, the Rho family GTPase CDC42, and the cytoskeletal organising complex Arp2/3 is probably critical to many of these functions, which when disturbed translate into measurable defects of cell signalling, polarization, motility, and phagocytosis. These recent findings provide additional clues as to the nature of the immunodeficiency of WAS, and ultimately may guide the development of more diverse and effective therapeutic strategies.