译者：蓝皮鼠

Platelet biogenesis and functions require correct protein O-glycosylation.

Proc Natl Acad Sci U S A 2012 Oct 2;109(40):16143-8 PMID:22988088 查看当期期刊

Wang Y,Jobe SM,Ding X,Choo H,Archer DR,Mi R,Ju T,Cummings RD

Departments of Biochemistry and Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.

Blood Platelets; Glycoproteins; Molecular Chaperones; Polysaccharides; Thrombocytopenia

Platelets express a variety of membrane and secreted glycoproteins, but the importance of glycosylation to platelet functions is poorly understood. To explore the importance of O-glycosylation, we generated mice with a targeted deletion of Cosmc in murine endothelial/hematopoietic cells (EHC) (EHC Cosmc(-/y)). X-linked Cosmc encodes an essential chaperone that regulates protein O-glycosylation. This targeted mutation resulted in lethal perinatal hemorrhage in the majority of mice, and the surviving mice displayed severely prolonged tail-bleeding times and macrothrombocytopenia. EHC Cosmc(-/y) platelets exhibited a marked decrease in GPIb-IX-V function and agonist-mediated integrin IIb 3 activation, associated with loss of interactions with von Willebrand factor and fibrinogen, respectively. Significantly, three O-glycosylated glycoproteins, GPIb , IIb, and GPVI normally on platelet surfaces that play essential roles in platelet functions, were partially proteolyzed in EHC Cosmc(-/y) platelets. These results demonstrate that extended O-glycans are required for normal biogenesis of the platelets as well as the expression and functions of their essential glycoproteins, and that variations in O-glycosylation may contribute to altered hemostasis.

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