A truncation variant of the cation channel P2RX5 is upregulated during T cell activation

• Published in: PloS one Vol. 9; no. 9; p. e104692
• Main Authors: Abramowski, Pierre, Ogrodowczyk, Christoph, Martin, Roland, Pongs, Olaf
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02.09.2014; Public Library of Science (PLoS)
• Subjects: Alternative splicing; Alternative Splicing - genetics; Amino acids; Animals; Biology and Life Sciences; Cardiac muscle; Cations; CD4 antigen; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - secretion; Cell activation; Cell Membrane - metabolism; Cell Polarity; Cell surface; Channels; Clonal deletion; Clone Cells; Cytokines; Deletion mutant; Diabetes; Gene expression; Gene Expression Profiling; Gene Knockdown Techniques; Genomes; Heart diseases; HEK293 Cells; Humans; Immunology; Immunoregulation; Interleukin 10; Interleukin-10 - secretion; Isoforms; Leukocytes; Ligands; Lymphocyte Activation - immunology; Lymphocyte Subsets - immunology; Lymphocytes; Lymphocytes T; Medical research; Medicine and Health Sciences; Multiple sclerosis; Muscles; Mutant Proteins - metabolism; Protein Subunits - genetics; Protein Subunits - metabolism; Protein Transport; Receptors, Purinergic P2X5 - genetics; Receptors, Purinergic P2X5 - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Signaling; siRNA; T cell receptors; T cells; Up-Regulation - genetics; White blood cells; Zebrafish; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0104692

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.