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.
Shcherbina
A
A
The Center for Blood Research and the Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Bretscher
A
A
Rosen
F S
FS
Kenney
D M
DM
Remold-O'Donnell
E
E
D001792:Blood Platelets / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015539:Platelet Activation; D011480:Protease Inhibitors / Q000494:pharmacology; D014923:Wiskott-Aldrich Syndrome / Q000097:blood* / Q000473:pathology
D008840:Microfilament Proteins; D011480:Protease Inhibitors; C071058:moesin