The Wiskott-Aldrich syndrome protein (WASP): Roles in signaling and cytoskeletal organization

The Wiskott-Aldrich Syndrome (WAS) is a rare X-linked primary immunodeficie ncy that is characterized by recurrent infections, hematopoietic malignanci es, eczema, and thrombocytopenia. A variety of hematopoietic cells are affe cted by the genetic defect, including lymphocytes, neutrophils, monocytes, and platelets. Early studies noted both signaling and cytoskeletal abnormal ities in lymphocytes from WAS patients. Following the identification of WAS P, the gene mutated in patients with this syndrome, and the more generally expressed WASP homologue N-WASP, studies have demonstrated that WASP-family molecules associate with numerous signaling molecules known to alter the a ctin cytoskeleton. WASP/N-WASP may depolymerize actin directly and/or serve as an adaptor or scaffold for these signaling molecules in a complex casca de that regulates the cytoskeleton.