The cytoskeletal linker protein moesin: decreased levels in Wiskott-Aldrich syndrome platelets and identification of a cleavage pathway in normal platelets

The Wiskott-Aldrich syndrome (WAS) is a severe disease of platelets (small size, thrombocytopenia) and lymphocytes (immunodeficiency) arising from mut ations of the X-chromosome gene WASP. Because of the prominent role of cyto skeletal abnormalities, particularly the paucity of surface microvilli, in the cellular pathology of this disease, blood cells from WAS patients were examined for moesin, a cytoskeletal linker protein that stabilizes cell sur face microvilli, filopodia and lamellipodia. Comparison of patient and norm al lymphocytes by immunofluorescence microscopy and immunoblotting showed n ormal levels and distribution of moesin in lymphocytes of WAS patients. In contrast, platelets from WAS patients stained only dimly for moesin relativ e to normal platelets. Quantitation by immunoblot revealed significantly de creased moesin levels in WAS patient platelets relative to normal platelets (63.5 +/- 4.9% of normal levels, n=8, P < 0.0001). A novel reaction of nor mal platelets was discovered that may play a role in the depletion of moesi n in patient platelets, namely the cleavage of moesin as a late event in pl atelet activation in response to certain platelet agonists.