C terminus of the P2X7 receptor: treasure hunting

Abstract

P2X receptor (P2XR) is a family of the ATPgated ion channel family and can permeabilize the plasma membrane to small cations such as potassium, sodium, and calcium, resulting in cellular depolarization. There are seven P2XR that have been described and cloned, with 45% identity in amino acid sequence. Each P2X receptors has two transmembrane domains that are separated by an extracellular loop and an intracellular N and C terminus. Unlike the other P2X receptors, the P2X7R has a larger C terminus with an extra 200 amino acid residues compared with the other receptors. The C terminus of the P2X7R has been implicated in regulating receptor function including signaling pathway activation, cellular localization, proteinprotein interactions, and post-translational modification (PTM). In the present review, we discuss the role of the P2X7R C terminus in regards to receptor function, describe the specific domains and motifs found therein and compare the C terminus sequence with others proteins to discover predicted domains or sites of PTM.

Hyperglycemia-induced Renal P2X7 Receptor Activation Enhances Diabetes-related Injury

“…There are seven P2X receptors that when activated by ATP, function as non-selective cation channels (Costa-Junior et al, 2011). The P2X7 receptor (P2X7R) has a uniquely long carboxyl domain that interacts with membrane pores such as pannexin-1 - to drive inflammation, cell death, and tissue remodelling (Lister et al, 2007, Menzies et al, 2015b).…”

Lipopolysaccharide Induces Alveolar Macrophage Necrosis via CD14 and the P2X7 Receptor Leading to Interleukin-1α Release

“…P2X7 receptors are a family of ATP gated ion channels that make the plasma membrane permeable to small cations such as Ca 2+ , resulting in cellular depolarization (Costa-Junior et al, 2011), and they have gained recent attention due to their ability to induce Ca 2+ mobility (Garcia-Marcos et al, 2006). P2X7R is expressed in most immune cells (Volonte et al, 2012), and its expression rapidly increases in alveolar macrophages (AM) following smoke-induced lung inflammation (Lucattelli et al, 2011).…”

Emerging key roles for P2X receptors in the kidney

“…Unlike its other family members it is thought to exist only as a homomer and has an extended C-terminus with 200 extra amino acid residues, which is thought to be pivotal in regulating its function, being involved in: determining cellular localization, stimulation of various signaling cascades, protein-protein interactions, and post-translational modification of the receptor itself (Costa-Junior et al, 2011). Sustained stimulation of P2X7R with high agonist concentrations (mM) is classically associated with the formation of large transmembrane pores that disrupt the ion gradients within cells resulting in subsequent cell death by either apoptosis or necrosis (Surprenant et al, 1996).…”

“…Sustained stimulation of P2X7R with high agonist concentrations (mM) is classically associated with the formation of large transmembrane pores that disrupt the ion gradients within cells resulting in subsequent cell death by either apoptosis or necrosis (Surprenant et al, 1996). The P2X7R is typically expressed by immune cells and mediates release of pro-inflammatory cytokines, prominently interleukin-1 beta (IL-1β), via activation of caspase 1 (Ferrari et al, 1997; Costa-Junior et al, 2011). In contrast to the healthy kidney in which P2X7R is virtually undetected, P2X7R expression is readily detected in inflammatory renal diseases, such as glomerulonephritis (Vonend et al, 2004).…”