The P2X7 receptor directly interacts with the NLRP3 inflammasome scaffold protein
Open accessAbstract
The P2X7 receptor (P2X7R) is a known and powerful activator of the NOD‐like receptor (NLR)P3 inflammasome; however, the underlying pathways are poorly understood. Thus, we investigated the molecular mechanisms involved. The effect of P2X7R expression and activation on NLRP3 expression and recruitment was investigated by Western blot, RT‐PCR, coimmunoprecipitation, and confocal microscopy in microglial mouse cell lines selected for reduced P2X7R expression and in primary cells from P2X7R ‐/‐ C57BL/6 mice. We show here that P2X7R activation by ATP (EC 50 = 1 mM) or benzoyl‐ATP (EC 50 = 300 μM) and P2X7R down‐modulation caused a 2‐ to 8‐fold up‐regulation of NLRP3 mRNA in mouse N13 microglial cells. Moreover, NLRP3 mRNA was also up‐regulated in primary microglial and macrophage cells from P2X7R ‐/‐ mice. Confocal microscopy and immunoprecipitation assays showed that P2X7R and NLRP3 closely interacted at discrete subplasmalemmal sites. Finally, P2X7R stimulation caused a transient (3‐4 min) cytoplasmic Ca 2+ increase localized to small (2‐3 μm wide) discrete subplasmalemmal regions. The Ca 2+ increase drove P2X7R recruitment and a 4‐fold increase in P2X7R/NLRP3 association within 1‐2 min. These data show a close P2X7R and NLRP3 interaction and highlight the role of P2X7R in the localized cytoplasmic ion changes responsible for both NLRP3 recruitment and activation.— Franceschini, A., Capece, M., Chiozzi, P., Falzoni, S., Sanz, J. M., Sarti, A. C., Bonora, M., Pinton, P., Di Virgilio, F. The P2X7 receptor directly interacts with the NLRP3 inflammasome scaffold protein. FASEB J. 29, 2450‐2461 (2015). www.fasebj.org
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P2RX7 has been linked to inflammasome activation.
“the latter of which has been linked to inflammasome activation58,59”
From INPP5D regulates inflammasome activation in human microglia (2023) · cites this paper as [59]
The paper title in our copy states that P2X7 directly interacts with the NLRP3 inflammasome scaffold protein, supporting a link to the inflammasome. The available passages do not state that this interaction activates the inflammasome; searches for activation returned only the title and repository metadata (no page number available). (LLM, conf=0.78)
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References 31 · Cited by 225
- Authors
- Franceschini, A., Capece, M., Chiozzi, P., Falzoni, S., Sanz, J. M., Sarti, A. C., Bonora, M., Pinton, P., & Di Virgilio, F.
- Affiliations
- University of Ferrara (IT)
- Department of Medical Sciences, Section of Internal Medicine, Gerontology, and Clinical Nutrition University of Ferrara Ferrara Italy
- Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology University of Ferrara Ferrara Italy
- ORCID
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2015-02-17
- Volume
- 29
- Issue
- 6
- Pages
- 2450-2461
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2155373881
- Cited by
- 225
- References
- 31
- Citations by year
- 2026: 9 · 2025: 27 · 2024: 17 · 2023: 26 · 2022: 22 · 2021: 23 · 2020: 17 · 2019: 20 · 2018: 21 · 2017: 24 · 2016: 15 · 2015: 4
- FWCI
- 17.97
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion, other-oa)
- Funders
- Associazione Italiana per la Ricerca sul Cancro (IG 5354, IG 14442)
- Università degli Studi di Ferrara
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Keywords
- P2X7 receptor, NLRP3 inflammasome, NOD-like receptors, ATP, microglia, macrophages, purinergic signaling, inflammasome activation
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Adenosine Triphosphate, Animals, Calcium, Carrier Proteins, Cell Line, Cells, Cultured, Cytoplasm, Gene Expression Regulation, Humans, Macrophages, Mice, Inbred C57BL, Protein Binding, Blotting, Western, Up-Regulation, Microglia, Mice, Knockout, Microscopy, Confocal, Reverse Transcriptase Polymerase Chain Reaction, HEK293 Cells, Receptors, Purinergic P2X7, Inflammasomes
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