Role of glycoprotein Ibα mobility in platelet function

Dianne E. van der Wal; Sandra Verhoef; Roger E. G. Schutgens; Marjolein Peters; Yaping Wu; Jan Willem N. Akkerman

doi:10.1160/TH09-11-0751

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2010; 103(05): 1033-1043
DOI: 10.1160/TH09-11-0751

Platelets and Blood Cells

Schattauer GmbH

Role of glycoprotein Ibα mobility in platelet function

Dianne E. van der Wal

¹Department of Clinical Chemistry and Haematology, University Medical Centre Utrecht, Utrecht, The Netherlands

,

Sandra Verhoef

¹Department of Clinical Chemistry and Haematology, University Medical Centre Utrecht, Utrecht, The Netherlands

,

Roger E. G. Schutgens

²Department of Haematology, University Medical Centre Utrecht, Utrecht, The Netherlands

,

Marjolein Peters

³Department of Pediatric-Haematology, Emma Childrens Hospital, Academic Medical Center Amsterdam

,

Yaping Wu

¹Department of Clinical Chemistry and Haematology, University Medical Centre Utrecht, Utrecht, The Netherlands

,

Jan Willem N. Akkerman

¹Department of Clinical Chemistry and Haematology, University Medical Centre Utrecht, Utrecht, The Netherlands

› Author Affiliations

Abstract

Summary

Incubation at 0°C is known to expose β-N-acetyl-D-glucosamine residues on glycoprotein (GP) Ibα inducing receptor clustering and α_Mβ₂-mediated platelet destruction by macrophages. Here we show that incubation at 0/37°C (4 hours at 0°C, followed by 1 hour at 37°C to mimic cold-storage and post-transfusion conditions) triggers a conformational change in the N-terminal flank (NTF, amino acids, aa 1–35) but not in aa 36–282 of GPIbα as detected by antibody binding. Addition of the sugar N-acetyl-D-glucosamine (GN) inhibits responses induced by 0/37°C. Incubation at 0°C shifts GPIbα from the membrane skeleton to the cytoskeleton. Different GPIbα conformations have little effect on VWF/ristocetin-induced aggregation, but arrest of NTF change by GN interferes with agglutination and spreading on a VWF-coated surface under flow. Strikingly, incubation at 0/37°C initiates thromboxane A₂ formation through a von Willebrand factor (VWF)-independent and GPIbα-dependent mechanism, as confirmed in VWF- and GPIbαﺹdeficient platelets. We conclude that the NTF change induced by 0/37°C incubation reflects clustering of GPIbα supports VWF/ristocetin-induced agglutination and spreading and is sufficient to initiate platelet activation in the absence of VWF.

Keywords

Glycoprotein Ibα - cold-storage - cytoskeleton - platelet - thromboxane A₂

Full Text

References

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