Alboluxin, a Snake C-type Lectin from Trimeresurus albolabris Venom is a Potent Platelet Agonist acting via GPIb and GPVI

Xiao-Yan Du; Edith Magnenat; Timothy N. C. Wells; Kenneth J. Clemetson

doi:10.1055/s-0037-1613067

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2002; 87(04): 692-698
DOI: 10.1055/s-0037-1613067

Review Article

Schattauer GmbH

Alboluxin, a Snake C-type Lectin from Trimeresurus albolabris Venom is a Potent Platelet Agonist acting via GPIb and GPVI

Xiao-Yan Du

¹Theodor Kocher Institute, University of Berne, Berne, Switzerland

,

Edith Magnenat

²Serono Pharmaceutical Research Institute SA, Plan-les-Ouates, Geneva, Switzerland

,

Timothy N. C. Wells

²Serono Pharmaceutical Research Institute SA, Plan-les-Ouates, Geneva, Switzerland

,

Kenneth J. Clemetson

¹Theodor Kocher Institute, University of Berne, Berne, Switzerland

› Institutsangaben

Abstract

Summary

Alboluxin, a potent platelet activator, was purified from Trimeresurus albolabris venom with a mass of 120 kDa non-reduced and, after reduction, subunits of 17 and 24 kDa. Alboluxin induced a tyrosine phosphorylation profile in platelets that resembles those produced by collagen and convulxin, involving the time dependent tyrosine phosphorylation of Fc receptor γ chain (Fcγ), phospholipase Cγ2 (PLCγ2), LAT and p72^SYK. Antibodies against both GPIb and GPVI inhibited platelet aggregation induced by alboluxin, whereas antibodies against α₂β₁ had no effect. Inhibition of α_IIbβ₃ reduced the aggregation response to alboluxin, as well as tyrosine phosphorylation of platelet proteins, showing that activation of α_IIbβ₃ and binding of fibrinogen are involved in alboluxin-induced platelet aggregation and it is not simply agglutination. N-terminal sequence data from the β-subunit of alboluxin indicates that it belongs to the snake C-type lectin family. The C-type lectin subunits are larger than usual possibly due to post-translational modifications such as glycosylation. Alboluxin is a hexameric (αβ)₃ snake C-type lectin which activates platelets via both GPIb and GPVI.

Keywords

Alboluxin - platelet aggregation - GPIb - GPVI - tyrosine phosphorylation

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