Platelet secretion and aggregation as well as thrombus formation of blood platelets critically depend on increase of cytosolic Ca2++ concentration ([Ca2++]i) mainly resulting from intracellular Ca2++ release followed by store operated Ca2++ entry (SOCE) through Ca2++ release activated channels (CRAC). SOCE is in part accomplished by the pore forming unit Orai and its regulator stromal interaction molecule (STIM). Orai1 and STIM1 transcription is stimulated by NF-κB (nuclear factor kappa B). Serum- and glucocorticoid-inducible kinase 1 (SGK1) up-regulates NF-κB-activity in megakaryocytes and thus Orai1- expression and SOCE in platelets. SGK1 is thus a powerful regulator of platelet Ca2++-signalling and thrombus formation and presumably participates in the regulation of platelet activation by a variety of hormones as well as clinical conditions (e.g. type 2 diabetes or metabolic syndrome) associated with platelet hyperaggregability and increased risk of thromboocclusive events. SOCE in platelets is further regulated by scaffolding protein Homer and chaperone protein cyclophilin A (CyPA). Additional potential regulators of Orai1/STIM1 and thus SOCE in platelets include AMP activated kinase (AMPK), protein kinase A (PKA), reactive oxygen species, lipid rafts, pH and mitochondrial Ca2++ buffering. Future studies are required defining the significance of those mechanisms for platelet Orai1 abundance and function, for SOCE into platelets and for platelet function in cardiovascular diseases. © Schattauer 2013.
CITATION STYLE
Lang, F., Münzer, P., Gawaz, M., & Borst, O. (2013). Regulation of STIM1/Orai1-dependent Ca2+ signalling in platelets. Thrombosis and Haemostasis, 110(5), 925–930. https://doi.org/10.1160/TH13-02-0176
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