RDF/XMLNTriplesTurtleShow queryShare
SubjectPredicateObject
http://purl.uniprot.org/citations/31964805http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/31964805http://www.w3.org/2000/01/rdf-schema#comment"Cells sense extracellular nucleotides through the P2Y class of purinergic G protein-coupled receptors (GPCRs), which stimulate integrin activation through signaling events, including intracellular Ca2+ mobilization. We investigated the relationship between P2Y-stimulated repetitive Ca2+ waves and fibrinogen binding to the platelet integrin αIIbβ3 (GPIIb/IIIa) through confocal fluorescence imaging of primary rat megakaryocytes. Costimulation of the receptors P2Y1 and P2Y12 generated a series of Ca2+ transients that each induced a rapid, discrete increase in fibrinogen binding. The peak and net increase of individual fibrinogen binding events correlated with the Ca2+ transient amplitude and frequency, respectively. Using BAPTA loading and selective receptor antagonists, we found that Ca2+ mobilization downstream of P2Y1 was essential for ADP-evoked fibrinogen binding, whereas P2Y12 and the kinase PI3K were also required for αIIbβ3 activation and enhanced the number of Ca2+ transients. ADP-evoked fibrinogen binding was initially uniform over the cell periphery but subsequently redistributed with a polarity that correlated with the direction of the Ca2+ waves. Polarization of αIIbβ3 may be mediated by the actin cytoskeleton, because surface-bound fibrinogen is highly immobile, and its motility was enhanced by cytoskeletal disruption. In conclusion, spatial and temporal patterns of Ca2+ increase enable fine control of αIIbβ3 activation after cellular stimulation. P2Y1-stimulated Ca2+ transients coupled to αIIbβ3 activation only in the context of P2Y12 coactivation, thereby providing an additional temporal mechanism of synergy between these Gq- and Gi-coupled GPCRs."xsd:string
http://purl.uniprot.org/citations/31964805http://purl.org/dc/terms/identifier"doi:10.1126/scisignal.aav7354"xsd:string
http://purl.uniprot.org/citations/31964805http://purl.uniprot.org/core/author"Gibbins J.M."xsd:string
http://purl.uniprot.org/citations/31964805http://purl.uniprot.org/core/author"Mahaut-Smith M.P."xsd:string
http://purl.uniprot.org/citations/31964805http://purl.uniprot.org/core/author"Bye A.P."xsd:string
http://purl.uniprot.org/citations/31964805http://purl.uniprot.org/core/date"2020"xsd:gYear
http://purl.uniprot.org/citations/31964805http://purl.uniprot.org/core/name"Sci Signal"xsd:string
http://purl.uniprot.org/citations/31964805http://purl.uniprot.org/core/pages"eaav7354"xsd:string
http://purl.uniprot.org/citations/31964805http://purl.uniprot.org/core/title"Ca2+ waves coordinate purinergic receptor-evoked integrin activation and polarization."xsd:string
http://purl.uniprot.org/citations/31964805http://purl.uniprot.org/core/volume"13"xsd:string
http://purl.uniprot.org/citations/31964805http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/31964805
http://purl.uniprot.org/citations/31964805http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/31964805
http://purl.uniprot.org/uniprot/#_A0A0G2K470-mappedCitation-31964805http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/31964805
http://purl.uniprot.org/uniprot/#_A6I5T2-mappedCitation-31964805http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/31964805
http://purl.uniprot.org/uniprot/#_Q924S3-mappedCitation-31964805http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/31964805
http://purl.uniprot.org/uniprot/A6I5T2http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/31964805
http://purl.uniprot.org/uniprot/A0A0G2K470http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/31964805
http://purl.uniprot.org/uniprot/Q924S3http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/31964805