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http://purl.uniprot.org/citations/32332099http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/32332099http://www.w3.org/2000/01/rdf-schema#comment"G protein-coupled receptor signaling is required for the navigation of immune cells along chemoattractant gradients. However, chemoattractant receptors may couple to more than one type of heterotrimeric G protein, each of which consists of a Gα, Gβ, and Gγ subunit, making it difficult to delineate the critical signaling pathways. Here, we used knockout mouse models and time-lapse microscopy to elucidate Gα and Gβ subunits contributing to complement C5a receptor-mediated chemotaxis. Complement C5a-mediated chemokinesis and chemotaxis were almost completely abolished in macrophages lacking Gnai2 (encoding Gαi2), consistent with a reduced leukocyte recruitment previously observed in Gnai2-/- mice, whereas cells lacking Gnai3 (Gαi3) exhibited only a slight decrease in cell velocity. Surprisingly, C5a-induced Ca2+ transients and lamellipodial membrane spreading were persistent in Gnai2-/- macrophages. Macrophages lacking both Gnaq (Gαq) and Gna11 (Gα11) or both Gna12 (Gα12) and Gna13 (Gα13) had essentially normal chemotaxis, Ca2+ signaling, and cell spreading, except Gna12/Gna13-deficient macrophages had increased cell velocity and elongated trailing ends. Moreover, Gnaq/Gna11-deficient cells did not respond to purinergic receptor P2Y2 stimulation. Genetic deletion of Gna15 (Gα15) virtually abolished C5a-induced Ca2+ transients, but chemotaxis and cell spreading were preserved. Homozygous Gnb1 (Gβ1) deletion was lethal, but mice lacking Gnb2 (Gβ2) were viable. Gnb2-/- macrophages exhibited robust Ca2+ transients and cell spreading, albeit decreased cell velocity and impaired chemotaxis. In summary, complement C5a-mediated chemotaxis requires Gαi2 and Gβ2, but not Ca2+ signaling, and membrane protrusive activity is promoted by G proteins that deplete phosphatidylinositol 4,5-bisphosphate."xsd:string
http://purl.uniprot.org/citations/32332099http://purl.org/dc/terms/identifier"doi:10.1074/jbc.ra119.011984"xsd:string
http://purl.uniprot.org/citations/32332099http://purl.uniprot.org/core/author"Wilkie T.M."xsd:string
http://purl.uniprot.org/citations/32332099http://purl.uniprot.org/core/author"Innamorati G."xsd:string
http://purl.uniprot.org/citations/32332099http://purl.uniprot.org/core/author"Hanley P.J."xsd:string
http://purl.uniprot.org/citations/32332099http://purl.uniprot.org/core/author"Horsthemke M."xsd:string
http://purl.uniprot.org/citations/32332099http://purl.uniprot.org/core/author"Wettschureck N."xsd:string
http://purl.uniprot.org/citations/32332099http://purl.uniprot.org/core/author"Bachg A.C."xsd:string
http://purl.uniprot.org/citations/32332099http://purl.uniprot.org/core/author"Ambrosy B."xsd:string
http://purl.uniprot.org/citations/32332099http://purl.uniprot.org/core/author"Walbaum S."xsd:string
http://purl.uniprot.org/citations/32332099http://purl.uniprot.org/core/author"van den Bos E."xsd:string
http://purl.uniprot.org/citations/32332099http://purl.uniprot.org/core/date"2020"xsd:gYear
http://purl.uniprot.org/citations/32332099http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/32332099http://purl.uniprot.org/core/pages"7726-7742"xsd:string
http://purl.uniprot.org/citations/32332099http://purl.uniprot.org/core/title"Knockout mouse models reveal the contributions of G protein subunits to complement C5a receptor-mediated chemotaxis."xsd:string
http://purl.uniprot.org/citations/32332099http://purl.uniprot.org/core/volume"295"xsd:string
http://purl.uniprot.org/citations/32332099http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/32332099
http://purl.uniprot.org/citations/32332099http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/32332099
http://purl.uniprot.org/uniprot/#_A0A0A6YWA9-mappedCitation-32332099http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32332099
http://purl.uniprot.org/uniprot/#_A0A0G2JG40-mappedCitation-32332099http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32332099
http://purl.uniprot.org/uniprot/#_A0A0A6YXC2-mappedCitation-32332099http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32332099
http://purl.uniprot.org/uniprot/#_A0A0A6YXN0-mappedCitation-32332099http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32332099
http://purl.uniprot.org/uniprot/#_A0A077S2U6-mappedCitation-32332099http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32332099
http://purl.uniprot.org/uniprot/#_D3Z1M1-mappedCitation-32332099http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32332099