P2RX7 Membrane Protein Introduction

Introduction of P2RX7

The P2RX7 receptor is a member of the family of extracellular ATP (eATP)-gated ion channels expressed in immune cells, where its activation triggers the inflammatory cascade. Therefore, P2RX7 has been long investigated as a target in the treatment of infectious and inflammatory diseases. Subsequently, P2RX7 signaling has been documented in other physiological and pathological processes including pain, CNS and psychiatric disorders and cancers. Notably, targeted inhibition of P2RX7 is crucial as its global blockade reduces the immune and inflammatory responses, which has important anti-tumor effects in some types of malignancies. P2RX7 comprises intracellular N and C termini, two transmembrane domains and a large intervening extracellular region containing the ATP binding site.

Basic Information of P2RX7
Protein Name P2X purinoceptor 7
Gene Name P2RX7
Aliases P2X7, ATP receptor, P2Z receptor, Purinergic receptor
Organism Homo sapiens (Human)
UniProt ID Q99572
Transmembrane Times 0
Length (aa) 595

Function of P2RX7 Membrane Protein

Belonging to the ionotropic purinergic P2X subfamily, P2RX7 is trimeric ligand-gated ion channel displaying a preference for cations and is responsible for the eATP-dependent lysis of macrophages. P2RX7 is to be expressed on macrophages and microglia with high levels, suggesting its role in regulating innate and adaptive immune responses. In addition, various researches have demonstrated that P2RX7 has a huge functional repertoire such as inflammation, proliferation, migration and invasion, metabolism, autophagy, cell death, and neurotransmission. P2RX7 over-expression and over-activation have been implicated in numerous physiological/pathophysiological processes. Specifically, P2RX7 regulates the immune response either directly or via Toll-like receptors (TLRs), and it has been reported that TLR2 and TLR4 can directly interact with P2RX7 via biglycan. Once activated by ATP, P2RX7 can trigger the TLR4-mediated pro-IL-1β processing followed by potassium efflux, NLRP3/ASC inflammasome assembly, and caspase-1-dependent IL-1β maturation and release. Besides, nearly all tumor types are found to have upregulated P2RX7 expression, highlighting the significant potential for novel therapeutic approaches.

Recent P2RX7 structural developments: the ATP binding pocket and the allosteric groove. Fig.1 Recent P2RX7 structural developments: the ATP binding pocket and the allosteric groove. (Young, 2018)

Application of P2RX7 Membrane Protein in Literature

  1. Borges da Silva H., et al. The purinergic receptor P2RX7 directs metabolic fitness of long-lived memory CD8(+) T cells. Nature. 2018, 559: 264-268. PubMed ID: 29973721

    In this article, the authors show that activation of P2RX7 by eATP can alert the nervous and immune system to tissue damage, and promote the metabolic fitness and survival of the most durable and functionally relevant memory CD8+ T cell populations.

  2. Yang R., et al. Tet1 and Tet2 maintain mesenchymal stem cell homeostasis via demethylation of the P2rX7 promoter. Nat Commun. 2018, 9: 2143. PubMed ID: 29858571

    This article indicates that Tet1 and Tet2 play a critical role in maintaining bone marrow mesenchymal stem cells (BMMSC) and bone homeostasis through demethylation of P2rX7 to control exosome and miRNA release, suggesting that Tet/P2rX7/Runx2 cascade may serve as a target for the development of novel therapies for osteopenic disorders.

  3. Zhang H., et al. Effect of Icariin on Tibial Dyschondroplasia Incidence and Tibial Characteristics by Regulating P2RX7 in Chickens. Biomed Res Int. 2018, 6796271. PubMed ID: 29750168

    This report suggests that icariin has a significant role in promoting the recovery of chicken growth plates affected by Tibial dyschondroplasia (TD) via regulating the P2RX7, revealing a new target for clinical treatment and prevention of TD in broiler chickens.

  4. Kim J.E., et al. P2RX7-MAPK1/2-SP1 axis inhibits MTOR independent HSPB1-mediated astroglial autophagy. Cell Death Dis. 2018, 9: 546. PubMed ID: 29749377

    This article suggests that P2RX7 may play an important role in the regulation of autophagy by the fine-tuning of HSPB1 expression.

  5. Al-Khalidi R., et al. Zidovudine ameliorates pathology in the mouse model of Duchenne muscular dystrophy via P2RX7 purinoceptor antagonism. Acta Neuropathol Commun. 2018, 6: 27. PubMed ID: 29642926

    This report reveals that AZT (Zidovudine) could inhibit P2RX7 functions, suggesting its potential role in the treatment of Duchenne muscular dystrophy (DMD). And it is not constrained by causative DMD mutations and may be effective in alleviating both muscle and non-muscle abnormalities.

P2RX7 Preparation Options

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  1. Young C N J and Gorecki D C. (2018). P2RX7 Purinoceptor as a Therapeutic Target-The Second Coming? Front Chem. 6: 248.

All listed customized services & products are for research use only, not intended for pharmaceutical, diagnostic, therapeutic or any in vivo human use.

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