P2X7 receptors regulate multiple types of membrane trafficking responses and non-classical secretion pathways

Abstract

Activation of the P2X7 receptor (P2X7R) triggers a remarkably diverse array of membrane trafficking responses in leukocytes and epithelial cells. These responses result in altered profiles of cell surface lipid and protein composition that can modulate the direct interactions of P2X7R-expressing cells with other cell types in the circulation, in blood vessels, at epithelial barriers, or within sites of immune and inflammatory activation. Additionally, these responses can result in the release of bioactive proteins, lipids, and large membrane complexes into extracellular compartments for remote communication between P2X7R-expressing cells and other cells that amplify or modulate inflammation, immunity, and responses to tissue damages. This review will discuss P2X7R-mediated effects on membrane composition and trafficking in the plasma membrane (PM) and intracellular organelles, as well as actions of P2X7R in controlling various modes of nonclassical secretion. It will review P2X7R regulation of: (1) phosphatidylserine distribution in the PM outer leaflet; (2) shedding of PM surface proteins; (3) release of PM-derived microvesicles or microparticles; (4) PM blebbing; (5) cell-cell fusion resulting in formation of multinucleate cells; (6) phagosome maturation and fusion with lysosomes; (7) permeability of endosomes with internalized pathogen-associated molecular patterns; (8) permeability/integrity of mitochondria; (9) exocytosis of secretory lysosomes; and (10) release of exosomes from multivesicular bodies.

Chemotherapeutic Drugs Induce ATP Release via Caspase-gated Pannexin-1 Channels and a Caspase/Pannexin-1-independent Mechanism

“…Whole cell lysates were prepared by detergentbased extractions prior to standard processing by SDS-PAGE (12% polyacrylamide), transfer to PVDF membranes, and Western blot analysis as described previously (26). Primary antibodies were used at the following concentrations or dilutions: anti-human Panx1 serum (1:5000), anti-PARP (0.05 g/ml), and anti-actin (1 g/ml).…”

Exosomes as intercellular signalosomes and pharmacological effectors

“…Among receptor-mediated exosome release, the GPCR-type receptor related to adenosine triphosphate (ATP)-gated ion channels, namely P2X7 receptor, susceptible to rapid changes in ionic fluxes, regulate the release of exosomes in immune and inflammatory effector cells [43 ].…”

The P2X7 receptor mediates the uptake of organic cations in canine erythrocytes and mononuclear leukocytes: comparison to equivalent human cell types

“…P2X 7 receptors are ligand-gated ion channels comprised of trimeric subunits within the plasma membrane [1] that interact with intracellular macromolecules [2] to regulate various membrane and intracellular responses [3]. Activation of P2X 7 by adenosine 5′-triphosphate (ATP) or the most potent agonist, 2′-and 3′-0(4-benzoylbenzoyl) ATP (BzATP) results in the movement of K + , Ca 2+ , Na + and large organic cations across the plasma membrane [4].…”