Defective platelet activation in Gα_q-deficient mice

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 α-subunit of the heterotrimeric guanine-nucleotide-binding protein Gq are unresponsive to a variety of physiological platelet activators. As a result, G α_q-deficient mice have increased bleeding times and are protected from collagen and adrenaline-induced thromboembolism. We conclude that G α_q is essential for the signalling processes used by different platelet activators and that it cannot be replaced by G α_i or the βγ subunits of the heterotrimeric G proteins. G α_q may thus be a new target for drugs designed to block the activation of platelets