title: Regulation of Platelet Function by Orai, STIM and TRP.
abstract: Agonist-induced changes in cytosolic Ca(2+) concentration ([Ca(2+)]c) are central events in platelet physiology. A major mechanism supporting agonist-induced Ca(2+) signals is store-operated Ca(2+) entry (SOCE), where the Ca(2+) sensor STIM1 and the channels of the Orai family, as well as TRPC members are the key elements. STIM1-dependent SOCE plays a major role in collagen-stimulated Ca(2+) signaling, phosphatidylserine exposure and thrombin generation. Furthermore, studies involving Orai1 gain-of-function mutants and platelets from Orai1-deficient mice have revealed the importance of this channel in thrombosis and hemostasis to those found in STIM1-deficient mice indicating that SOCE might play a prominent role in thrombus formation. Moreover, increase in TRPC6 expression might lead to thrombosis in humans. The role of STIM1, Orai1 and TRPCs, and thus SOCE, in thrombus formation, suggests that therapies directed against SOCE and targeting these molecules during cardiovascular and cerebrovascular events could significantly improve traditional anti-thrombotic treatments.
authors.affiliation: Laboratory of Molecular Physiology and Channelopathies, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, 08003, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Berna-Erro
authors.affiliation: Department of Physiology (Cell Physiology Research Group), University of Extremadura, Cáceres, 10003, Spain.
authors.forename: Isaac
authors.initials: I
authors.lastname: Jardín
authors.affiliation: Department of Medical Physiology and Biophysic, Institute of Biomedicine of Seville (IBiS), University Hospital of Virgen del Rocío/CSIC/University of Seville, Sevilla, 41013, Spain.
authors.forename: Tarik
authors.initials: T
authors.lastname: Smani
authors.affiliation: Departamento de Fisiología, University of Extremadura, Cáceres, Spain. jarosado@unex.es.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Rosado
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D015220:Calcium Channels / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D000071737:Stromal Interaction Molecule 1; D050052:TRPC Cation Channels / Q000502:physiology*
chemical_list: D015220:Calcium Channels; C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1; D050052:TRPC Cation Channels
keywords: Calcium entry; Human platelets; Orai1; STIM1; TRPC1; TRPC6