Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
A functional P2X7 splice variant with an alternative transmembrane domain 1 escapes gene inactivation in P2X7 knock-out mice.
Nicke A
,
Kuan YH
,
Masin M
,
Rettinger J
,
Marquez-Klaka B
,
Bender O
,
Górecki DC
,
Murrell-Lagnado RD
,
Soto F
.
???displayArticle.abstract???
The ATP-activated P2X7 receptor channel is involved in immune function and inflammatory pain and represents an important drug target. Here we describe a new P2X7 splice variant (P2X7(k)), containing an alternative intracellular N terminus and first transmembrane domain encoded by a novel exon 1 in the rodent P2rx7 gene. Whole cell patch clamp recordings of the rat isoform expressed in HEK293 cells revealed an 8-fold higher sensitivity to the agonist Bz-ATP and much slower deactivation kinetics when compared with the P2X7(a) receptor. Permeability measurements in Xenopus oocytes show a high permeability for N-methyl-D-glucamine immediately upon activation, suggesting that the P2X7(k) channel is constitutively dilated upon opening. The rates of agonist-induced dye uptake and membrane blebbing in HEK cells were also increased. PCR analyses and biochemical analysis by SDS-PAGE and BN-PAGE indicate that the P2X7(k) variant escapes gene deletion in one of the available P2X7(-/-) mice strains and is strongly expressed in the spleen. Taken together, we describe a novel P2X7 isoform with distinct functional properties that contributes to the diversity of P2X7 receptor signaling. Its presence in one of the P2X7(-/-) strains has important implications for our understanding of the role of this receptor in health and disease.
Amstrup,
P2X7 receptor activates extracellular signal-regulated kinases ERK1 and ERK2 independently of Ca2+ influx.
2003, Pubmed
Amstrup,
P2X7 receptor activates extracellular signal-regulated kinases ERK1 and ERK2 independently of Ca2+ influx.
2003,
Pubmed
Anderson,
Emerging challenges of assigning P2X7 receptor function and immunoreactivity in neurons.
2006,
Pubmed
Barrera,
Atomic force microscopy imaging demonstrates that P2X2 receptors are trimers but that P2X6 receptor subunits do not oligomerize.
2005,
Pubmed
Boué-Grabot,
A protein kinase C site highly conserved in P2X subunits controls the desensitization kinetics of P2X(2) ATP-gated channels.
2000,
Pubmed
,
Xenbase
Burge,
Prediction of complete gene structures in human genomic DNA.
1997,
Pubmed
Cabrini,
A His-155 to Tyr polymorphism confers gain-of-function to the human P2X7 receptor of human leukemic lymphocytes.
2005,
Pubmed
Chaumont,
Patch-clamp coordinated spectroscopy shows P2X2 receptor permeability dynamics require cytosolic domain rearrangements but not Panx-1 channels.
2008,
Pubmed
Cheewatrakoolpong,
Identification and characterization of splice variants of the human P2X7 ATP channel.
2005,
Pubmed
Chessell,
Disruption of the P2X7 purinoceptor gene abolishes chronic inflammatory and neuropathic pain.
2005,
Pubmed
Di Virgilio,
Nucleotide receptors: an emerging family of regulatory molecules in blood cells.
2001,
Pubmed
Donnelly-Roberts,
Discovery of P2X7 receptor-selective antagonists offers new insights into P2X7 receptor function and indicates a role in chronic pain states.
2007,
Pubmed
Duan,
P2X(7) receptors: properties and relevance to CNS function.
2006,
Pubmed
Feng,
A truncated P2X7 receptor variant (P2X7-j) endogenously expressed in cervical cancer cells antagonizes the full-length P2X7 receptor through hetero-oligomerization.
2006,
Pubmed
He,
A simplified system for generating recombinant adenoviruses.
1998,
Pubmed
Hong,
Differential regulation of P2X7 receptor activation by extracellular nicotinamide adenine dinucleotide and ecto-ADP-ribosyltransferases in murine macrophages and T cells.
2009,
Pubmed
Jiang,
N-methyl-D-glucamine and propidium dyes utilize different permeation pathways at rat P2X(7) receptors.
2005,
Pubmed
Ke,
Deletion of the P2X7 nucleotide receptor reveals its regulatory roles in bone formation and resorption.
2003,
Pubmed
Khakh,
Neuronal P2X transmitter-gated cation channels change their ion selectivity in seconds.
1999,
Pubmed
Khakh,
Contribution of transmembrane regions to ATP-gated P2X2 channel permeability dynamics.
2005,
Pubmed
Kim,
Differential assembly of rat purinergic P2X7 receptor in immune cells of the brain and periphery.
2001,
Pubmed
Klapperstück,
Functional evidence of distinct ATP activation sites at the human P2X(7) receptor.
2001,
Pubmed
,
Xenbase
Labasi,
Absence of the P2X7 receptor alters leukocyte function and attenuates an inflammatory response.
2002,
Pubmed
Lucae,
P2RX7, a gene coding for a purinergic ligand-gated ion channel, is associated with major depressive disorder.
2006,
Pubmed
Mackenzie,
Pseudoapoptosis induced by brief activation of ATP-gated P2X7 receptors.
2005,
Pubmed
Marquez-Klaka,
Identification of an intersubunit cross-link between substituted cysteine residues located in the putative ATP binding site of the P2X1 receptor.
2007,
Pubmed
,
Xenbase
Masin,
Fe65 interacts with P2X2 subunits at excitatory synapses and modulates receptor function.
2006,
Pubmed
Nicke,
P2X1 and P2X3 receptors form stable trimers: a novel structural motif of ligand-gated ion channels.
1998,
Pubmed
,
Xenbase
Nicke,
Biochemical and functional evidence for heteromeric assembly of P2X1 and P2X4 subunits.
2005,
Pubmed
,
Xenbase
North,
Molecular physiology of P2X receptors.
2002,
Pubmed
Ohlendorff,
Single nucleotide polymorphisms in the P2X7 gene are associated to fracture risk and to effect of estrogen treatment.
2007,
Pubmed
Ormond,
An uncharged region within the N terminus of the P2X6 receptor inhibits its assembly and exit from the endoplasmic reticulum.
2006,
Pubmed
Paukert,
The P2X(7) receptor from Xenopus laevis: formation of a large pore in Xenopus oocytes.
2002,
Pubmed
,
Xenbase
Pelegrin,
Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor.
2006,
Pubmed
Roger,
Facilitation of P2X7 receptor currents and membrane blebbing via constitutive and dynamic calmodulin binding.
2008,
Pubmed
Schägger,
Analysis of molecular masses and oligomeric states of protein complexes by blue native electrophoresis and isolation of membrane protein complexes by two-dimensional native electrophoresis.
1994,
Pubmed
Sharp,
P2x7 deficiency suppresses development of experimental autoimmune encephalomyelitis.
2008,
Pubmed
Shemon,
A Thr357 to Ser polymorphism in homozygous and compound heterozygous subjects causes absent or reduced P2X7 function and impairs ATP-induced mycobacterial killing by macrophages.
2006,
Pubmed
,
Xenbase
Sim,
Reanalysis of P2X7 receptor expression in rodent brain.
2004,
Pubmed
Solle,
Altered cytokine production in mice lacking P2X(7) receptors.
2001,
Pubmed
Soto,
P2X4: an ATP-activated ionotropic receptor cloned from rat brain.
1996,
Pubmed
,
Xenbase
Surprenant,
The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7).
1996,
Pubmed
Sánchez-Nogueiro,
Characterization of a functional P2X(7)-like receptor in cerebellar granule neurons from P2X(7) knockout mice.
2005,
Pubmed
Taylor,
Lymphocytes from P2X7-deficient mice exhibit enhanced P2X7 responses.
2009,
Pubmed
Tsukimoto,
P2X7 receptor-dependent cell death is modulated during murine T cell maturation and mediated by dual signaling pathways.
2006,
Pubmed
Vial,
G-protein-coupled receptor regulation of P2X1 receptors does not involve direct channel phosphorylation.
2004,
Pubmed
,
Xenbase
Virginio,
Pore dilation of neuronal P2X receptor channels.
1999,
Pubmed
Virginio,
Kinetics of cell lysis, dye uptake and permeability changes in cells expressing the rat P2X7 receptor.
1999,
Pubmed
Yan,
The P2X7 receptor channel pore dilates under physiological ion conditions.
2008,
Pubmed
