Defective platelet activation in G alpha sub(q)-deficient mice

• Published in: Nature (London) 1997-09, Vol.389 (6647), p.183-186
• Main Authors: Offermanns, S, Toombs, C F, Hu, Yi-Hui, Simon, MI
• Format: Article
• Language: English
• ISSN: 0028-0836

Platelets are small disc-shaped cell fragments which undergo a rapid transformation when they encounter vascular damage. They become more spherical and extrude pseudopodia, their fibrinogen receptors are activated, causing them to aggregate, they release their granule contents, and eventually form a plug which is responsible for primary haemostasis. Activation of platelets is also implicated in the pathogenesis of unstable angina, myocardial infarction and stroke. Here we show that platelets from mice deficient in the alpha -subunit of the heterotrimeric guanine-nucleotide-binding protein G sub(q) are unresponsive to a variety of physiological platelet activators. As a result, G alpha sub(q)-deficient mice have increased bleeding times and are protected from collagen and adrenaline-induced thromboembolism. We conclude that G alpha sub(q) is essential for the signalling processes used by different platelet activators and that it cannot be replaced by G alpha sub(i) or the beta gamma subunits of the heterotrimeric G proteins. G alpha sub(q) may thus be a new target for drugs designed to block the activation of platelets.