Dianne M. Kenney

Moesin, the major ERM protein of lymphocytes and platelets, differs from ezrin in its insensitivity to calpain.

The ERM proteins, ezrin, radixin and moesin, provide regulated linkage of the cytoskeleton with the plasma membrane, particularly in cell surface projections. Ezrin and moesin were found co‐expressed, and radixin was not detected, in human blood lymphocytes, monocytes and neutrophils. Moesin is the quantitatively dominant ERM protein in these cells and the only one in platelets. Because Ca2+ signaling pathways involving calpain cleavages are important in blood cells, we examined ERM protein sensitivity to this protease. A striking difference was discovered: sensitivity of ezrin and resistance of moesin (and radixin) to calpain. In intact stimulated lymphocytes, ezrin was cleaved, while moesin was not, strongly suggesting that differential sensitivity to calpain contributes to specialized functions of these proteins.

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 mutations of the X‐chromosome gene WASP. Because of the prominent role of cytoskeletal 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 surface microvilli, filopodia and lamellipodia. Comparison of patient and normal lymphocytes by immunofluorescence microscopy and immunoblotting showed normal levels and distribution of moesin in lymphocytes of WAS patients. In contrast, platelets from WAS patients stained only dimly for moesin relative to normal platelets. Quantitation by immunoblot revealed significantly decreased 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 normal platelets was discovered that may play a role in the depletion of moesin in patient platelets, namely the cleavage of moesin as a late event in platelet activation in response to certain platelet agonists.