Proceedings of the National Academy of Sciences · 2020 · 108 citations · 70 references
Life SciencesCell BiologyMolecular BiologyCell SignalingHemostasisSignal TransductionG Protein-coupled Receptor SignalingPlatelet ActivationPlatelet AdhesionPlatelet AggregationPlatelet FunctionPlatelet PhysiologyBlood FlowCell Surface Area ExpansionCollagen-mediated Platelet ActivationG Protein-coupled Receptor ActivationHemostatic Plug FormationPlatelet Plug FormationPlatelet Surface ReceptorsShear-dependent Platelet Adhesion
Significance We identified the known collagen receptor GPR56/ADGRG1 on platelets. GPR56 is an adhesion G protein-coupled receptor that becomes activated following forced dissociation of its N-terminal fragment and C-terminal fragment or seven-transmembrane spanning domain (7TM). Fragment dissociation reveals the cryptic stalk of the 7TM, which acts as a tethered peptide agonist, and for GPR56, this activates platelet G13 signaling. GPR56 pharmacological probes activated platelets to undergo shape change and aggregation, which are critical for the formation of hemostatic plugs. Gpr56 −/− mice exhibit prolonged bleeding, defective platelet plug formation in vessel injury assays, and delayed thrombotic vessel occlusion. Shear-force dependency of platelet adhesion to immobilized collagen was found to be GPR56 dependent.
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G Protein-Coupled Receptor-Dependent Development of Human Frontal Cortex
Xianhua Piao, R. Sean Hill, Adria Bodell et al. · Science · 2004 · 522 citations