DEFECTIVE ACTIN POLYMERIZATION IN EBV-TRANSFORMED B-CELL LINES FROM PATIENTS WITH THE WISKOTT-ALDRICH-SYNDROME

The Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive disord er characterized by eczema, thrombocytopenia, and immunodeficiency. An allelic variant of the disease is characterized by isolated thrombocy topenia (XLT), The gene responsible for WAS/XLT (WASP) encodes for a 5 02 amino acid protein (WASP) that is possibly involved in actin bindin g and cytoskeleton organization. The expression of WASP and the distri bution of F-actin and alpha-actinin (which binds to and stabilizes act in filaments) have been analysed in lymphoblastoid cell lines from six patients with WAS and one with XLT, Western blot and immunocytochemis try did not reveal WASP expression in four WAS patients, whereas two W AS patients (with a moderate clinical course) expressed trace amounts of mutant WASP. In contrast, the XLT patient expressed normal amounts of WASP, Furthermore, cell lines from WAS and XLT patients also marked ly differed in F-actin polymerization and alpha-actinin distribution, In particular, severe defects of cytoplasmic F-actin expression and of F-actin-positive microvillus formation, and impaired capping of alpha -actinin, mere observed in all patients who lacked WASP. As a whole, t he degree of impairment of WASP protein expression in WAS/XLT seems to correlate with anomalies of cytoskeletal organization, strongly suppo rting a role for WASP in the regulation of F-actin polymerization, (C) 1998 John Wiley & Sons, Ltd.