GPIb is involved in platelet aggregation induced by mucetin, a snake C-type lectin protein from Chinese habu (Trimeresurus mucrosquamatus) venom

Lu, Qiumin; Navdaev, Alexei; Clemetson, Jeannine; Clemetson, Kenneth John (2004). GPIb is involved in platelet aggregation induced by mucetin, a snake C-type lectin protein from Chinese habu (Trimeresurus mucrosquamatus) venom. Thrombosis and haemostasis, 91(6), pp. 1168-1176. Stuttgart: Schattauer 10.1160/TH03-12-0747

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Mucetin (Trimeresurus mucrosquamatus venom activator, TMVA) is a potent platelet activator purified from Chinese habu (Trimeresurus mucrosquamatus) venom. It belongs to the snake venom heterodimeric C-type lectin family and exists in several multimeric forms. We now show that binding to platelet glycoprotein (GP) Ib is involved in mucetin-induced platelet aggregation. Antibodies against GPIb as well as the GPIb-blocking C-type lectin echicetin inhibited mucetin-induced platelet aggregation. Binding of GPIb was confirmed by affinity chromatography and Western blotting. Antibodies against GPVI inhibited convulxin- but not mucetin-induced aggregation. Signalling by mucetin involved rapid tyrosine phosphorylation of a number of proteins including Syk, Src, LAT and PLC gamma 2. Mucetin-induced phosphorylation of the Fc gamma chain of platelet was greatly promoted by inhibition of alpha(IIb)beta(3) by the peptidomimetic EMD 132338, suggesting that phosphatases downstream of alpha(IIb)beta(3) activation are involved in dephosphorylation of Fc gamma. Unlike other multimeric snake C-type lectins that act via GPIb and only agglutinate platelets, mucetin activates alpha(IIb)beta(3). Inhibition of alpha(IIb)beta(3) strongly reduced the aggregation response to mucetin, indicating that activation of alpha(IIb)beta(3) and binding of fibrinogen are involved in mucetin-induced platelet aggregation. Apyrase and aspirin also inhibit platelet aggregation induced by mucetin, suggesting that ADP and thromboxane A2 are involved in autocrine feedback. Sequence and structural comparison with closely related members of this protein family point to features that may be responsible for the functional differences.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Navdaev, Alexei; Clemetson, Jeannine and Clemetson, Kenneth John

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0340-6245

ISBN:

15175804

Publisher:

Schattauer

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:52

Last Modified:

27 Oct 2019 01:22

Publisher DOI:

10.1160/TH03-12-0747

PubMed ID:

15175804

Web of Science ID:

000222113600015

BORIS DOI:

10.7892/boris.22193

URI:

https://boris.unibe.ch/id/eprint/22193 (FactScience: 32240)

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