Programme and Abstracts of the 68th National Congress of the Italian Physiological Society (Società Italiana di Fisiologia) (Abstract) The SLC15A4 gene codes for the peptide/histidine transporter 1 (PHT1), a carrier of di/tripeptides and histidine. In vertebrates, the SLC15A4 genes are mainly expressed by the immune and nervous systems, in which they are acknowledged to undergo splicing events of unknown physiological meaning. After the early generic detection of the canonical SLC15A4/PHT1 isoforms on plasma and subcellular membranes, recent studies have pointed out that the human SLC15A4 gene codes for a late endosome/lysosome transmembrane carrier taking part in TLR7-, TLR9-, and NOD1-mediated pathways, thus suggesting that its gene products may act as regulators of inflammatory/immune/autoimmune onsets and diseases. Accordingly, SLC15A4/PHT1 altered activity has been associated to conditions such as type 2 diabetes, inflammatory bowel diseases (IBD) and systemic lupus erythematosus. Here, we report the description of a unique alternative splicing-mediated regulation of the SLC15A4 gene, conserved from zebrafish to human. We demonstrate that this regulation is physiologically facilitated by the Nonsense-Mediated mRNA Decay (NMD) surveillance system, in human immune-derived cells too, and that it is sensitive to inflammatory molecular triggers. Furthermore, in an IBD murine model induced with the inflammatory challenge by dextran sulfate sodium, we describe its impact on the expression of the alternative SLC15A4 gene products, revealing their differential modulations in different GI tracts.
Peptide/histidine transporter 1 (SLC15A4) gene products under physiological or inflammatory challenges: insights from the mammalian GI.
Barca A;Mazzei A;Del Vecchio G;Pisani P;Verri T.
2017-01-01
Abstract
Programme and Abstracts of the 68th National Congress of the Italian Physiological Society (Società Italiana di Fisiologia) (Abstract) The SLC15A4 gene codes for the peptide/histidine transporter 1 (PHT1), a carrier of di/tripeptides and histidine. In vertebrates, the SLC15A4 genes are mainly expressed by the immune and nervous systems, in which they are acknowledged to undergo splicing events of unknown physiological meaning. After the early generic detection of the canonical SLC15A4/PHT1 isoforms on plasma and subcellular membranes, recent studies have pointed out that the human SLC15A4 gene codes for a late endosome/lysosome transmembrane carrier taking part in TLR7-, TLR9-, and NOD1-mediated pathways, thus suggesting that its gene products may act as regulators of inflammatory/immune/autoimmune onsets and diseases. Accordingly, SLC15A4/PHT1 altered activity has been associated to conditions such as type 2 diabetes, inflammatory bowel diseases (IBD) and systemic lupus erythematosus. Here, we report the description of a unique alternative splicing-mediated regulation of the SLC15A4 gene, conserved from zebrafish to human. We demonstrate that this regulation is physiologically facilitated by the Nonsense-Mediated mRNA Decay (NMD) surveillance system, in human immune-derived cells too, and that it is sensitive to inflammatory molecular triggers. Furthermore, in an IBD murine model induced with the inflammatory challenge by dextran sulfate sodium, we describe its impact on the expression of the alternative SLC15A4 gene products, revealing their differential modulations in different GI tracts.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
