GPR56/ADGRG1 is a platelet collagen-responsive GPCR and hemostatic sensor of shear force

• DOI: 10.1073/pnas.2008921117
• Publication Date: 2020-10-24T00:30:34Z
• Authors: Jennifer Yeung; Reheman Adili; Emily N. Stringham; Rong Luo; Alexander Vizurraga; Luciana K. Rossel...; Hannah M. Stoveken; Maiya Yu; Xianhua Piao; Michael Holinstat; Gregory G. Tall
• Keywords: Blood Platelets; Mice, Knockout; 0301 basic medicine; Hemostasis; Integrins; Platelet Aggregation; Thrombosis; Biological Sciences; Receptors, G-Protein-Coupled; Mice; 03 medical and health sciences; Platelet Adhesiveness; Animals; Humans; Collagen; Pseudopodia; Transcriptome; Signal Transduction

Circulating platelets roll along exposed collagen at vessel injury sites and respond with filipodia protrusion, shape change, surface area expansion to facilitate platelet adhesion plug formation. Various glycoproteins were considered be both responders mediators of adhesion, yet the signaling kinetics emanating from these receptors do not fully account for rapid cytoskeletal changes that occur in blood flow. We found free N-terminal fragment G protein-coupled receptor (GPCR) GPR56 human plasma report is transduces signals flow-induced shear force activate protein 13 change. Gpr56-/- mice have prolonged bleeding, defective formation, delayed thrombotic occlusion. Human mouse perfusion studies demonstrated shear-force dependence immobilized collagen. Our work places as an initial responder transducer essential change during hemostasis.