Cited by 280Adenosine and Purinergic SignalingCalcium signaling and nucleotide metabolismIon Channels and Receptors

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The Elusive P2X7 Macropore

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Di Virgilio, Francesco, Schmalzing, Günther, Markwardt, Fritz·2018·Trends in Cell Biology

DOI 10.1016/j.tcb.2018.01.005

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Abstract

ATP, which is released under pathological conditions and is considered a damage-associated molecular pattern (DAMP), activates P2X7 receptors (P2X7Rs), trimeric plasma membrane ion channels selective for small cations. P2X7Rs are partners in NOD-like receptor containing a pyrin (NLRP3) inflammasome activation and promoters of tumor cell growth. P2X7R overstimulation triggers the ATP-dependent opening of a nonselective plasma membrane pore, known as a 'macropore', which allows fluxes of large hydrophilic molecules. The pathophysiological functions of P2X7R are thought to be dependent on activation of this conductance pathway, yet its molecular identity is unknown. Recent reports show that P2X7R permeability to organic solutes is an early and intrinsic property of the channel itself. A better understanding of P2X7R-dependent changes in plasma membrane permeability will allow a rationale development of novel anti-inflammatory and anticancer drugs.

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Authors: Di Virgilio, F., Schmalzing, G., & Markwardt, F.
Affiliations: RWTH Aachen University (DE)
Venue: Trends in Cell Biology
Publisher: Elsevier BV
Published: 2018-05
Volume: 28
Issue: 5
Pages: 392-404
ISSN: 0962-8924 (ISSN-L)
DOI: 10.1016/j.tcb.2018.01.005
OpenAlex: W2787249947
Cited by: 279
References: 96
Citations by year: 2026: 23 · 2025: 22 · 2024: 41 · 2023: 44 · 2022: 31 · 2021: 30 · 2020: 33 · 2019: 37 · 2018: 17
FWCI: 3.44
Type: journal article
Language: en
Open access: green
www.sciencedirect.com
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Trends in Cell Biology (publishedVersion)
PubMed (publishedVersion)
RWTH Publications (RWTH Aachen) (submittedVersion)
Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion, cc-by-nc-nd)
Funders: Italian Association for Cancer Research (13025, 18581)
Ministry of Health of Italy (RF-2011-02348435)
University of Ferrara
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
Keywords: P2X7 receptor, ATP, plasma membrane permeability, NLRP3 inflammasome, damage-associated molecular patterns, ion channel conductance, anti-inflammatory agents, anticancer agents
MeSH terms: Alarmins, NLR Family, Pyrin Domain-Containing 3 Protein, Adenosine Triphosphate, Cell Membrane Permeability, Humans, Neoplasms, Signal Transduction, Cell Proliferation, Receptors, Purinergic P2X7, Inflammasomes

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