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Published on: March 11, 2022
Platelet biogenesis and functions require correct protein O-glycosylation
Yingchun Wang1, Shawn M Jobe, Xiaokun Ding
1Departments of Biochemistry and Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Summary
Altered O-glycosylation in platelets impairs their function and biogenesis. This study reveals extended O-glycans are crucial for platelet glycoproteins and hemostasis.
Area of Science:
- Biochemistry
- Hematology
- Molecular Biology
Background:
- Platelet glycoproteins are essential for hemostasis, but the role of glycosylation in their function is unclear.
- O-glycosylation, a critical post-translational modification, is vital for protein structure and function.
Purpose of the Study:
- To investigate the role of O-glycosylation in platelet biogenesis and function.
- To determine the impact of Cosmc deletion on platelet glycoproteins and hemostasis.
Main Methods:
- Generated mice with targeted deletion of Cosmc (regulator of O-glycosylation) in endothelial/hematopoietic cells (EHC Cosmc(-/y)).
- Assessed platelet count, bleeding times, glycoprotein function (GPIb-IX-V, integrin αIIbβ3), and protein integrity.
Main Results:
- EHC Cosmc(-/y) mice exhibited lethal perinatal hemorrhage, prolonged bleeding times, and macrothrombocytopenia.
- Platelets showed reduced GPIb-IX-V and integrin αIIbβ3 activation, with impaired von Willebrand factor and fibrinogen interactions.
- Key platelet glycoproteins (GPIbα, αIIb, GPVI) were partially proteolyzed due to loss of O-glycans.
Conclusions:
- Extended O-glycans are essential for proper platelet biogenesis and the expression/function of critical surface glycoproteins.
- Defective O-glycosylation significantly impacts platelet function and may contribute to hemostatic disorders.
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