title: A truncation variant of the cation channel P2RX5 is upregulated during T cell activation.
abstract: Members of the P2X family of ligand-gated cation channels (P2RX) are expressed by various cell types including neurons, smooth- and cardiac muscle cells, and leukocytes. The channels mediate signalling in response to extracellular ATP. Seven subunit isoforms (P2RX1-P2RX7) have been identified and these can assemble as homo- and heterotrimeric molecules. In humans, P2RX5 exists as a natural deletion mutant lacking amino acids 328-349 of exon 10, which are part of transmembrane (TM) 2 and pre-TM2 regions in other organisms like rat, chicken and zebrafish. We show that P2RX5 gene expression of human T lymphocytes is upregulated during activation. P2RX5 is recruited to the cell surface. P2RX5-siRNA-transfected CD4+ T cells produced twofold more IL-10 than controls. Surface and intracellular P2RX5 expression was upregulated in activated antigen-specific CD4+ T cell clones. These data indicate a functional role of the human P2RX5 splice variant in T cell activation and immunoregulation.
authors.affiliation: Institute for Neuroimmunology and Clinical Multiple Sclerosis Research (inims), ZMNH, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Research Department Cell and Gene Therapy, Clinic for Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Pierre
authors.initials: P
authors.lastname: Abramowski
authors.affiliation: Institute for Neural Signaltransduction, ZMNH, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Ogrodowczyk
authors.affiliation: Institute for Neuroimmunology and Clinical Multiple Sclerosis Research (inims), ZMNH, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Neuroimmunology and MS Research, Department of Neurology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Roland
authors.initials: R
authors.lastname: Martin
authors.affiliation: Institute for Neural Signaltransduction, ZMNH, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute for Physiology, University Hospital Homburg, Homburg/Saar, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Pongs
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D002999:Clone Cells; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology; D050505:Mutant Proteins / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D058485:Receptors, Purinergic P2X5 / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: D050505:Mutant Proteins; C546465:P2RX5 protein, human; D021122:Protein Subunits; D012333:RNA, Messenger; D058485:Receptors, Purinergic P2X5; D016753:Interleukin-10