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dc.contributor.authorBelloso Uribe, Kepa
dc.contributor.authorMartín Plágaro, César Augusto
dc.contributor.authorEtxebarria, Aitor
dc.contributor.authorGonzález Bullón, David ORCID
dc.contributor.authorGómez Bilbao, Geraxane
dc.contributor.authorOstolaza Echabe, Elena Amaya ORCID
dc.date.accessioned2014-02-06T19:42:04Z
dc.date.available2014-02-06T19:42:04Z
dc.date.issued2013-09
dc.identifier.citationPlos ONE 8(9) : 2013 // e74248es
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/10810/11378
dc.description.abstractHumans infected with Bordetella pertussis, the whooping cough bacterium, show evidences of impaired host defenses. This pathogenic bacterium produces a unique adenylate cyclase toxin (ACT) which enters human phagocytes and catalyzes the unregulated formation of cAMP, hampering important bactericidal functions of these immune cells that eventually cause cell death by apoptosis and/or necrosis. Additionally, ACT permeabilizes cells through pore formation in the target cell membrane. Recently, we demonstrated that ACT is internalised into macrophages together with other membrane components, such as the integrin CD11b/CD18 (CR3), its receptor in these immune cells, and GM1. The goal of this study was to determine whether ACT uptake is restricted to receptor-bearing macrophages or on the contrary may also take place into cells devoid of receptor and gain more insights on the signalling involved. Here, we show that ACT is rapidly eliminated from the cell membrane of either CR3-positive as negative cells, though through different entry routes, which depends in part, on the target cell physiology and characteristics. ACT-induced Ca2+ influx and activation of non-receptor Tyr kinases into the target cell appear to be common master denominators in the different endocytic strategies activated by this toxin. Very importantly, we show that, upon incubation with ACT, target cells are capable of repairing the cell membrane, which suggests the mounting of an anti-toxin cell repair-response, very likely involving the toxin elimination from the cell surface.es
dc.description.sponsorshipThis study was supported by grants from the Spanish Ministerio de Ciencia y Tecnologia (Project BFU 2007-62062 and Project BFU 2012-36241), the Basque Government (ETORTEK Program), and the University of Basque Country (UPV/EHU, Project UE06/10). KBU and GG were recipients of a fellowship from the Bizkaia Biophysics Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.es
dc.language.isoenges
dc.publisherPublic Library Publishinges
dc.relationinfo:eu-repo/grantAgreement/MCYT/BFU2007-62062
dc.relationinfo:eu-repo/grantAgreement/MINECO/BFU2012-36241
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.subjectreceptor mediated endocytosises
dc.subjectpore forming toxinses
dc.subjectendothelial cellses
dc.subjectbacillus anthracises
dc.subjectsignaling pathwayes
dc.subjectplasma mebranees
dc.subjectcalcium influxes
dc.subjectlipid raftses
dc.subjectcyclic ampes
dc.subjectpertussises
dc.titleCa2+ Influx and Tyrosine Kinases Trigger Bordetella Adenylate Cyclase Toxin (ACT) Endocytosis. Cell Physiology and Expression of the CD11b/CD18 Integrin Major Determinants of the Entry Routees
dc.typeinfo:eu-repo/semantics/articlees
dc.rights.holder© 2013 Uribe et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.es
dc.relation.publisherversionhttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0074248es
dc.identifier.doi10.1371/journal.pone.0074248
dc.departamentoesBioquímica y biología moleculares_ES
dc.departamentoeuBiokimika eta biologia molekularraes_ES
dc.subject.categoriaAGRICULTURAL AND BIOLOGICAL SCIENCES
dc.subject.categoriaMEDICINE
dc.subject.categoriaBIOCHEMISTRY AND MOLECULAR BIOLOGY


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