Identification and characterization of splice variants of the human P2X7 ATP channel.
The P2X7 channel is a member of the P2X family of ligand-gated ion channels which respond to ATP as the endogenous agonist. Studies suggest that P2X7 has a potentially pivotal role in inflammatory responses largely stemming from its role in mediating the release of IL-1beta in response to ATP. We report the identification of seven variants of human P2X7 which result from alternative splicing. Two of these variants (one lacking the first transmembrane domain, the second lacking the entire cytoplasmic tail) were compared to the full-length channel. Real-time PCR analysis demonstrated that both variants were expressed in various tissues and that the cytoplasmic tail deleted variant is highly expressed. Deletion of the first transmembrane domain resulted in a non-functional channel. Deletion of the cytoplasmic tail did not affect ion movement but severely affected the ability to form a large pore and to induce activation of caspases.
Cheewatrakoolpong
Boonlert
B
Department of Cardiovascular/Metabolism, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
Gilchrest
Helen
H
Anthes
John C
JC
Greenfeder
Scott
S
D000255:Adenosine Triphosphate / Q000378:metabolism*; D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D004274:DNA, Recombinant / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D007473:Ion Channels / Q000032:analysis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009928:Organ Specificity; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000032:analysis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
D004274:DNA, Recombinant; D007473:Ion Channels; C546468:P2RX7 protein, human; D020033:Protein Isoforms; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate