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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, OBJECTIVE, METHODS, RESULTS. Meshes: 14-3-3 Proteins, Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Antiphospholipid Syndrome, Autoantibodies, Biological Transport, Active, Blood Platelets, Dimerization, Humans, In Vitro Techniques, LDL-Receptor Related Proteins, Molecular Sequence Data, Nerve Tissue Proteins, Platelet Activation, Platelet Adhesiveness, Platelet Glycoprotein GPIb-IX Complex, Receptors, Lipoprotein, Signal Transduction, beta 2-Glycoprotein I.
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Does platelet activation by dimeric beta2-glycoprotein I require signaling via both glycoprotein Ibalpha and apolipoprotein E receptor 2 '? Context: Dimerization of beta(2)-glycoprotein I (beta(2)-GPI) by autoantibodies is thought to trigger the clinical manifestations observed in the antiphospholipid syndrome. Arterial thrombosis, a frequently occurring clinical manifestation of the antiphospholipid syndrome, is a process in which platelets play a crucial role. Previous work has shown that binding of dimeric beta(2)-GPI to the platelet receptors apolipoprotein E receptor 2' (ApoER2') and glycoprotein Ibalpha (GPIbalpha) mediates increased platelet activation in an in vitro thrombosis model. The individual roles of ApoER2' and GPIbalpha in mediating platelet activation by dimeric beta(2)-GPI has hitherto been unclear. In this study, we have determined the roles of either receptor in platelet activation by dimeric beta(2)-GPI. Platelet activation by dimeric beta(2)-GPI was studied under conditions of flow. Intracellular signaling induced by dimeric beta(2)-GPI was subsequently analyzed by means of sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) and western blot analysis. The increase in platelet deposition onto a fibronectin surface under conditions of flow by dimeric beta(2)-GPI was completely abolished by inhibition of the interaction of dimeric beta(2)-GPI with either GPIbalpha or ApoER2'. Upon platelet stimulation with dimeric beta(2)-GPI, GPIbalpha translocated to the cytoskeleton via the scaffold protein 14-3-3zeta. Concomitantly, ApoER2' dissociated from the adapter protein Disabled1, presumably through phosphorylation of the cytoplasmic tail. Inhibition of one process could not inhibit the other.
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We show that dimeric beta(2)-GPI signals via two distinct pathways in platelets, both of which are required for platelet activation. Abrogation of either signal results in loss of activation. Final Decision: yes