Different localization of P2X4 and P2X7 receptors in native mouse lung - lack of evidence for a direct P2X4-P2X7 receptor interaction
IntroductionP2X receptors are a family of homo- and heterotrimeric cation channels gated by extracellular ATP. The P2X4 and P2X7 subunits show overlapping expression patterns and have been involved in similar physiological processes, such as pain and inflammation as well as various immune cell funct...
| প্রধান লেখক: | , , , , , , , , , , , , , , |
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| বিন্যাস: | প্রবন্ধ |
| ভাষা: | English |
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Frontiers Media S.A.
2024-06-01
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| মালা: | Frontiers in Immunology |
| বিষয়গুলি: | |
| অনলাইন ব্যবহার করুন: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1425938/full |
| _version_ | 1827221471376703488 |
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| author | Juan Sierra-Marquez Lena Schaller Lukas Sassenbach Antonio Ramírez-Fernández Philipp Alt Björn Rissiek Béla Zimmer Johann Schredelseker Johann Schredelseker Julia Hector Tobias Stähler Friedrich Koch-Nolte Claudia A. Staab-Weijnitz Claudia A. Staab-Weijnitz Alexander Dietrich Robin Kopp Annette Nicke |
| author_facet | Juan Sierra-Marquez Lena Schaller Lukas Sassenbach Antonio Ramírez-Fernández Philipp Alt Björn Rissiek Béla Zimmer Johann Schredelseker Johann Schredelseker Julia Hector Tobias Stähler Friedrich Koch-Nolte Claudia A. Staab-Weijnitz Claudia A. Staab-Weijnitz Alexander Dietrich Robin Kopp Annette Nicke |
| author_sort | Juan Sierra-Marquez |
| collection | DOAJ |
| description | IntroductionP2X receptors are a family of homo- and heterotrimeric cation channels gated by extracellular ATP. The P2X4 and P2X7 subunits show overlapping expression patterns and have been involved in similar physiological processes, such as pain and inflammation as well as various immune cell functions. While formation of P2X2/P2X3 heterotrimers produces a distinct pharmacological phenotype and has been well established, functional identification of a P2X4/P2X7 heteromer has been difficult and evidence for and against a physical association has been found. Most of this evidence stems, however, from in vitro model systems.MethodsHere, we used a P2X7-EGFP BAC transgenic mouse model as well as P2X4 and P2X7 knock-out mice to re-investigate a P2X4-P2X7 interaction in mouse lung by biochemical and immunohistochemical experiments as well as quantitative expression analysis.ResultsNo detectable amounts of P2X4 could be co-purified from mouse lung via P2X7-EGFP. In agreement with these findings, immuno-histochemical analysis using a P2X7-specific nanobody revealed only limited overlap in the cellular and subcellular localizations of P2X4 and P2X7 in both the native lung tissue and primary cells. Comparison of P2X4 and P2X7 transcript and protein levels in the respective gene-deficient and wild type mice showed no mutual interrelation between their expression levels in whole lungs. However, a significantly reduced P2rx7 expression was found in alveolar macrophages of P2rx4-/- mice.DiscussionIn summary, our detailed analysis of the cellular and subcellular P2X4 and P2X7 localization and expression does not support a physiologically relevant direct association of P2X4 and P2X7 subunits or receptors in vivo. |
| first_indexed | 2025-03-21T16:23:07Z |
| format | Article |
| id | doaj.art-b55a6bb7bcc24c3691c0c6357b0bf403 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2025-03-21T16:23:07Z |
| publishDate | 2024-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b55a6bb7bcc24c3691c0c6357b0bf4032024-06-17T08:56:14ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-06-011510.3389/fimmu.2024.14259381425938Different localization of P2X4 and P2X7 receptors in native mouse lung - lack of evidence for a direct P2X4-P2X7 receptor interactionJuan Sierra-Marquez0Lena Schaller1Lukas Sassenbach2Antonio Ramírez-Fernández3Philipp Alt4Björn Rissiek5Béla Zimmer6Johann Schredelseker7Johann Schredelseker8Julia Hector9Tobias Stähler10Friedrich Koch-Nolte11Claudia A. Staab-Weijnitz12Claudia A. Staab-Weijnitz13Alexander Dietrich14Robin Kopp15Annette Nicke16Walther Straub Institute of Pharmacology and Toxicology, Member of the German Center for Lung Research (DZL), Faculty of Medicine, LMU Munich, Munich, GermanyWalther Straub Institute of Pharmacology and Toxicology, Member of the German Center for Lung Research (DZL), Faculty of Medicine, LMU Munich, Munich, GermanyWalther Straub Institute of Pharmacology and Toxicology, Member of the German Center for Lung Research (DZL), Faculty of Medicine, LMU Munich, Munich, GermanyWalther Straub Institute of Pharmacology and Toxicology, Member of the German Center for Lung Research (DZL), Faculty of Medicine, LMU Munich, Munich, GermanyWalther Straub Institute of Pharmacology and Toxicology, Member of the German Center for Lung Research (DZL), Faculty of Medicine, LMU Munich, Munich, GermanyDepartment of Neurology, University Medical Centre Hamburg-Eppendorf, Hamburg, GermanyWalther Straub Institute of Pharmacology and Toxicology, Member of the German Center for Lung Research (DZL), Faculty of Medicine, LMU Munich, Munich, GermanyWalther Straub Institute of Pharmacology and Toxicology, Member of the German Center for Lung Research (DZL), Faculty of Medicine, LMU Munich, Munich, GermanyDeutsches Zentrum für Herz-Kreislauf-Forschung, Partner Site Munich Heart Alliance, Munich, GermanyWalther Straub Institute of Pharmacology and Toxicology, Member of the German Center for Lung Research (DZL), Faculty of Medicine, LMU Munich, Munich, GermanyInstitute of Immunology, University Medical Centre Hamburg-Eppendorf, Hamburg, GermanyInstitute of Immunology, University Medical Centre Hamburg-Eppendorf, Hamburg, GermanyInstitute of Lung Health and Immunity (LHI), Helmholtz Munich, Comprehensive Pneumology Center (CPC-M), Member of the German Center for Lung Research (DZL), GermanyDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesWalther Straub Institute of Pharmacology and Toxicology, Member of the German Center for Lung Research (DZL), Faculty of Medicine, LMU Munich, Munich, GermanyWalther Straub Institute of Pharmacology and Toxicology, Member of the German Center for Lung Research (DZL), Faculty of Medicine, LMU Munich, Munich, GermanyWalther Straub Institute of Pharmacology and Toxicology, Member of the German Center for Lung Research (DZL), Faculty of Medicine, LMU Munich, Munich, GermanyIntroductionP2X receptors are a family of homo- and heterotrimeric cation channels gated by extracellular ATP. The P2X4 and P2X7 subunits show overlapping expression patterns and have been involved in similar physiological processes, such as pain and inflammation as well as various immune cell functions. While formation of P2X2/P2X3 heterotrimers produces a distinct pharmacological phenotype and has been well established, functional identification of a P2X4/P2X7 heteromer has been difficult and evidence for and against a physical association has been found. Most of this evidence stems, however, from in vitro model systems.MethodsHere, we used a P2X7-EGFP BAC transgenic mouse model as well as P2X4 and P2X7 knock-out mice to re-investigate a P2X4-P2X7 interaction in mouse lung by biochemical and immunohistochemical experiments as well as quantitative expression analysis.ResultsNo detectable amounts of P2X4 could be co-purified from mouse lung via P2X7-EGFP. In agreement with these findings, immuno-histochemical analysis using a P2X7-specific nanobody revealed only limited overlap in the cellular and subcellular localizations of P2X4 and P2X7 in both the native lung tissue and primary cells. Comparison of P2X4 and P2X7 transcript and protein levels in the respective gene-deficient and wild type mice showed no mutual interrelation between their expression levels in whole lungs. However, a significantly reduced P2rx7 expression was found in alveolar macrophages of P2rx4-/- mice.DiscussionIn summary, our detailed analysis of the cellular and subcellular P2X4 and P2X7 localization and expression does not support a physiologically relevant direct association of P2X4 and P2X7 subunits or receptors in vivo.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1425938/fullP2X7 receptorP2X4 receptorheteromerizationfunctional interactionlung epithelial cellsmacrophage |
| spellingShingle | Juan Sierra-Marquez Lena Schaller Lukas Sassenbach Antonio Ramírez-Fernández Philipp Alt Björn Rissiek Béla Zimmer Johann Schredelseker Johann Schredelseker Julia Hector Tobias Stähler Friedrich Koch-Nolte Claudia A. Staab-Weijnitz Claudia A. Staab-Weijnitz Alexander Dietrich Robin Kopp Annette Nicke Different localization of P2X4 and P2X7 receptors in native mouse lung - lack of evidence for a direct P2X4-P2X7 receptor interaction Frontiers in Immunology P2X7 receptor P2X4 receptor heteromerization functional interaction lung epithelial cells macrophage |
| title | Different localization of P2X4 and P2X7 receptors in native mouse lung - lack of evidence for a direct P2X4-P2X7 receptor interaction |
| title_full | Different localization of P2X4 and P2X7 receptors in native mouse lung - lack of evidence for a direct P2X4-P2X7 receptor interaction |
| title_fullStr | Different localization of P2X4 and P2X7 receptors in native mouse lung - lack of evidence for a direct P2X4-P2X7 receptor interaction |
| title_full_unstemmed | Different localization of P2X4 and P2X7 receptors in native mouse lung - lack of evidence for a direct P2X4-P2X7 receptor interaction |
| title_short | Different localization of P2X4 and P2X7 receptors in native mouse lung - lack of evidence for a direct P2X4-P2X7 receptor interaction |
| title_sort | different localization of p2x4 and p2x7 receptors in native mouse lung lack of evidence for a direct p2x4 p2x7 receptor interaction |
| topic | P2X7 receptor P2X4 receptor heteromerization functional interaction lung epithelial cells macrophage |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1425938/full |
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