title: The P2X7/P2X4 interaction shapes the purinergic response in murine macrophages.
abstract: The ATP-gated P2X4 and P2X7 receptors are cation channels, co-expressed in excitable and non-excitable cells and play important roles in pain, bone development, cytokine release and cell death. Although these receptors interact the interacting domains are unknown and the functional consequences of this interaction remain unclear. Here we show by co-immunoprecipitation that P2X4 interacts with the C-terminus of P2X7 and by fluorescence resonance energy transfer experiments that this receptor-receptor interaction is driven by ATP. Furthermore, disrupting the ATP-driven interaction by knocking-out P2X4R provoked an attenuation of P2X7-induced cell death, dye uptake and IL-1β release in macrophages. Thus, P2X7 interacts with P2X4 via its C-terminus and disrupting the P2X7/P2X4 interaction hinders physiological responses in immune cells.
authors.affiliation: School of Medicine, Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Pérez-Flores
authors.affiliation: Centre de Recherche du Centre Hospitalier Universitaire (CHU) de Québec-CHUL et Département de Médecine Moléculaire de Université Laval, Québec, QC, Canada.
authors.forename: Sébastien A
authors.initials: SA
authors.lastname: Lévesque
authors.affiliation: Institute of Cellular Physiology, UNAM, México City, Mexico.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Pacheco
authors.affiliation: Institute of Cellular Physiology, UNAM, México City, Mexico.
authors.forename: Luis
authors.initials: L
authors.lastname: Vaca
authors.affiliation: Centre de Recherche du Centre Hospitalier Universitaire (CHU) de Québec-CHUL et Département de Médecine Moléculaire de Université Laval, Québec, QC, Canada.
authors.forename: Steve
authors.initials: S
authors.lastname: Lacroix
authors.affiliation: School of Medicine, Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico.
authors.forename: Patricia
authors.initials: P
authors.lastname: Pérez-Cornejo
authors.affiliation: Physics Institute, Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico. Electronic address: arreola@dec1.ifisica.uaslp.mx.
authors.forename: Jorge
authors.initials: J
authors.lastname: Arreola
mesh_terms: D000818:Animals; D031541:Fluorescence Resonance Energy Transfer; D005456:Fluorescent Dyes; D057809:HEK293 Cells; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058848:Receptors, Purinergic P2X4 / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*
chemical_list: D005456:Fluorescent Dyes; D058848:Receptors, Purinergic P2X4; D058486:Receptors, Purinergic P2X7
keywords: Cell death; FRET; IL-1β; P2X4; P2X7; Patch clamp