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Biochem Biophys Res Commun. 2015 Nov 20;467(3):484-90. doi: 10.1016/j.bbrc.2015.10.025. Epub 2015 Oct 9.

The P2X7/P2X4 interaction shapes the purinergic response in murine macrophages.

Author information

1
School of Medicine, Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico.
2
Centre de Recherche du Centre Hospitalier Universitaire (CHU) de Québec-CHUL et Département de Médecine Moléculaire de Université Laval, Québec, QC, Canada.
3
Institute of Cellular Physiology, UNAM, México City, Mexico.
4
Physics Institute, Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico. Electronic address: arreola@dec1.ifisica.uaslp.mx.

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.

KEYWORDS:

Cell death; FRET; IL-1β; P2X4; P2X7; Patch clamp

PMID:
26456657
DOI:
10.1016/j.bbrc.2015.10.025
[Indexed for MEDLINE]

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