Tetherin/BST-2 negatively regulates other membrane microdomain–expressed receptor functions in mouse platelets. Thrombin (A)-, TP thromboxane (B)-, and CRP (C)-stimulated platelet aggregation was significantly enhanced in BST-2^−/− vs BST-2^+/+ mice in washed platelets. Representative traces from 3 independent experiments showing platelet aggregation (top) and ATP secretion (bottom) in response to thrombin in the absence and presence of the P2Y₁₂ receptor antagonist (ARC66096; 10 μM), U46619 or CRP. (D-E) Data were quantified and expressed as maximum aggregation (D) and ATP secretion (E). Data represent mean ± standard error of the mean (SEM) of 3 independent experiments. *P < .05; 2-tailed Student t test. (F) Platelet α-granule secretion was assessed by measuring thrombin (0.03 μ/mL)-stimulated P-selectin expression by flow cytometry. Data represent mean ± SEM of 3 independent experiments. *P < .05; 2-tailed Student t test.