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Structural and Functional Basis for Understanding the Biological Significance of P2X7 Receptor
The P2X7 receptor (P2X7R) possesses a unique structure associated to an as yet not fully understood mechanism of action that facilitates cell permeability to large ionic molecules through the receptor itself and/or nearby membrane proteins. High extracellular adenosine triphosphate (ATP) levels—inex...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696479/ https://www.ncbi.nlm.nih.gov/pubmed/33182829 http://dx.doi.org/10.3390/ijms21228454 |
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author | Martínez-Cuesta, María Ángeles Blanch-Ruiz, María Amparo Ortega-Luna, Raquel Sánchez-López, Ainhoa Álvarez, Ángeles |
author_facet | Martínez-Cuesta, María Ángeles Blanch-Ruiz, María Amparo Ortega-Luna, Raquel Sánchez-López, Ainhoa Álvarez, Ángeles |
author_sort | Martínez-Cuesta, María Ángeles |
collection | PubMed |
description | The P2X7 receptor (P2X7R) possesses a unique structure associated to an as yet not fully understood mechanism of action that facilitates cell permeability to large ionic molecules through the receptor itself and/or nearby membrane proteins. High extracellular adenosine triphosphate (ATP) levels—inexistent in physiological conditions—are required for the receptor to be triggered and contribute to its role in cell damage signaling. The inconsistent data on its activation pathways and the few studies performed in natively expressed human P2X7R have led us to review the structure, activation pathways, and specific cellular location of P2X7R in order to analyze its biological relevance. The ATP-gated P2X7R is a homo-trimeric receptor channel that is occasionally hetero-trimeric and highly polymorphic, with at least nine human splice variants. It is localized predominantly in the cellular membrane and has a characteristic plasticity due to an extended C-termini, which confers it the capacity of interacting with membrane structural compounds and/or intracellular signaling messengers to mediate flexible transduction pathways. Diverse drugs and a few endogenous molecules have been highlighted as extracellular allosteric modulators of P2X7R. Therefore, studies in human cells that constitutively express P2X7R need to investigate the precise endogenous mediator located nearby the activation/modulation domains of the receptor. Such research could help us understand the possible physiological ATP-mediated P2X7R homeostasis signaling. |
format | Online Article Text |
id | pubmed-7696479 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-76964792020-11-29 Structural and Functional Basis for Understanding the Biological Significance of P2X7 Receptor Martínez-Cuesta, María Ángeles Blanch-Ruiz, María Amparo Ortega-Luna, Raquel Sánchez-López, Ainhoa Álvarez, Ángeles Int J Mol Sci Review The P2X7 receptor (P2X7R) possesses a unique structure associated to an as yet not fully understood mechanism of action that facilitates cell permeability to large ionic molecules through the receptor itself and/or nearby membrane proteins. High extracellular adenosine triphosphate (ATP) levels—inexistent in physiological conditions—are required for the receptor to be triggered and contribute to its role in cell damage signaling. The inconsistent data on its activation pathways and the few studies performed in natively expressed human P2X7R have led us to review the structure, activation pathways, and specific cellular location of P2X7R in order to analyze its biological relevance. The ATP-gated P2X7R is a homo-trimeric receptor channel that is occasionally hetero-trimeric and highly polymorphic, with at least nine human splice variants. It is localized predominantly in the cellular membrane and has a characteristic plasticity due to an extended C-termini, which confers it the capacity of interacting with membrane structural compounds and/or intracellular signaling messengers to mediate flexible transduction pathways. Diverse drugs and a few endogenous molecules have been highlighted as extracellular allosteric modulators of P2X7R. Therefore, studies in human cells that constitutively express P2X7R need to investigate the precise endogenous mediator located nearby the activation/modulation domains of the receptor. Such research could help us understand the possible physiological ATP-mediated P2X7R homeostasis signaling. MDPI 2020-11-10 /pmc/articles/PMC7696479/ /pubmed/33182829 http://dx.doi.org/10.3390/ijms21228454 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Martínez-Cuesta, María Ángeles Blanch-Ruiz, María Amparo Ortega-Luna, Raquel Sánchez-López, Ainhoa Álvarez, Ángeles Structural and Functional Basis for Understanding the Biological Significance of P2X7 Receptor |
title | Structural and Functional Basis for Understanding the Biological Significance of P2X7 Receptor |
title_full | Structural and Functional Basis for Understanding the Biological Significance of P2X7 Receptor |
title_fullStr | Structural and Functional Basis for Understanding the Biological Significance of P2X7 Receptor |
title_full_unstemmed | Structural and Functional Basis for Understanding the Biological Significance of P2X7 Receptor |
title_short | Structural and Functional Basis for Understanding the Biological Significance of P2X7 Receptor |
title_sort | structural and functional basis for understanding the biological significance of p2x7 receptor |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696479/ https://www.ncbi.nlm.nih.gov/pubmed/33182829 http://dx.doi.org/10.3390/ijms21228454 |
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