QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: mol.107.035980v1 72/6/1447    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Related articles in MolPharm Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Guo, C. Articles by Murrell-Lagnado, R. D. Search for Related Content PubMed PubMed Citation Articles by Guo, C. Articles by Murrell-Lagnado, R. D.

Evidence for Functional P2X₄/P2X₇ Heteromeric Receptors

Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom

The cytolytic ionotropic ATP receptor P2X₇ has several important roles in immune cell regulation, such as cytokine release, apoptosis, and microbial killing. Although P2X₇ receptors are frequently coexpressed with another subtype of P2X receptor, P2X₄, they are believed not to form heteromeric assemblies but to function only as homomers. Both receptors play a role in neuropathic pain; therefore, understanding how they coordinate the cellular response to ATP is important for the development of effective pain therapies. Here, we provide biochemical and electrophysiological evidence for an association between P2X₄ and P2X₇ that increases the diversity of receptor currents mediated via these two subtypes. The heterologously expressed receptors were coimmunoprecipitated from human embryonic kidney (HEK) 293 cells, and the endogenous P2X₄ and P2X₇ receptors were similarly coimmunoprecipitated from bone marrow-derived macrophages. In HEK293 cells, the fraction of P2X₄ receptors biotinylated at the plasma membrane increased 2-fold in the presence of P2X₇ although there was no change in overall expression. Coexpression of a dominant-negative P2X₄ mutant (C353W) with P2X₇, inhibited P2X₇ receptor mediated currents by greater than 2-fold, whereas a nonfunctional but non–dominant-negative mutant (S341W) did not. Coexpression of P2X₄S341W with P2X₇ produced a current that was potentiated by ivermectin and inhibited by 2',3'-O-(2,4,6-trinitrophenyl) adenosine 5-triphosphate (TNP-ATP), whereas expression of P2X₇ alone produced a current that was insensitive to both of these compounds at the concentrations used. These results demonstrate a structural and functional interaction between P2X₄ and P2X₇, which suggests that they associate to form heteromeric receptors.

Related articles in MolPharm:

Go It Alone No More—P2X7 Joins the Society of Heteromeric ATP-Gated Receptor Channels

George R. Dubyak
MolPharm 2007 72: 1402-1405. [Abstract] [Full Text]  

This article has been cited by other articles:

				R. Murrell-Lagnado More cross-talk between purinergic receptors J. Physiol., June 15, 2009; 587(12): 2713 - 2714. [Full Text] [PDF]

				G. Casas-Pruneda, J. P. Reyes, G. Pérez-Flores, P. Pérez-Cornejo, and J. Arreola Functional interactions between P2X4 and P2X7 receptors from mouse salivary epithelia J. Physiol., June 15, 2009; 587(12): 2887 - 2901. [Abstract] [Full Text] [PDF]

				S. R. J. Taylor, M. Gonzalez-Begne, D. K. Sojka, J. C. Richardson, S. A. Sheardown, S. M. Harrison, C. D. Pusey, F. W. K. Tam, and J. I. Elliott Lymphocytes from P2X7-deficient mice exhibit enhanced P2X7 responses J. Leukoc. Biol., June 1, 2009; 85(6): 978 - 986. [Abstract] [Full Text] [PDF]

				M. Boumechache, M. Masin, J. M. Edwardson, D. C. Gorecki, and R. Murrell-Lagnado Analysis of Assembly and Trafficking of Native P2X4 and P2X7 Receptor Complexes in Rodent Immune Cells J. Biol. Chem., May 15, 2009; 284(20): 13446 - 13454. [Abstract] [Full Text] [PDF]

				M. Skals, N. R. Jorgensen, J. Leipziger, and H. A. Praetorius {alpha}-Hemolysin from Escherichia coli uses endogenous amplification through P2X receptor activation to induce hemolysis PNAS, March 10, 2009; 106(10): 4030 - 4035. [Abstract] [Full Text] [PDF]

				T. Nakamoto, D. A. Brown, M. A. Catalan, M. Gonzalez-Begne, V. G. Romanenko, and J. E. Melvin Purinergic P2X7 Receptors Mediate ATP-induced Saliva Secretion by the Mouse Submandibular Gland J. Biol. Chem., February 20, 2009; 284(8): 4815 - 4822. [Abstract] [Full Text] [PDF]

				Y. Fujiwara, B. Keceli, K. Nakajo, and Y. Kubo Voltage- and [ATP]-dependent Gating of the P2X2 ATP Receptor Channel J. Gen. Physiol., January 1, 2009; 133(1): 93 - 109. [Abstract] [Full Text] [PDF]

				L.-P. Bernier, A. R. Ase, S. Chevallier, D. Blais, Q. Zhao, E. Boue-Grabot, D. Logothetis, and P. Seguela Phosphoinositides Regulate P2X4 ATP-Gated Channels through Direct Interactions J. Neurosci., November 26, 2008; 28(48): 12938 - 12945. [Abstract] [Full Text] [PDF]

				D. Donnelly-Roberts, S. McGaraughty, C.-C. Shieh, P. Honore, and M. F. Jarvis Painful Purinergic Receptors J. Pharmacol. Exp. Ther., February 1, 2008; 324(2): 409 - 415. [Abstract] [Full Text] [PDF]

				G. R. Dubyak Go It Alone No More P2X7 Joins the Society of Heteromeric ATP-Gated Receptor Channels Mol. Pharmacol., December 1, 2007; 72(6): 1402 - 1405. [Abstract] [Full Text] [PDF]