title: A glutathione peroxidase, intracellular peptidases and the TOR complexes regulate peptide transporter PEPT-1 in C. elegans.
abstract: The intestinal peptide transporter PEPT-1 in Caenorhabditis elegans is a rheogenic H(+)-dependent carrier responsible for the absorption of di- and tripeptides. Transporter-deficient pept-1(lg601) worms are characterized by impairments in growth, development and reproduction and develop a severe obesity like phenotype. The transport function of PEPT-1 as well as the influx of free fatty acids was shown to be dependent on the membrane potential and on the intracellular pH homeostasis, both of which are regulated by the sodium-proton exchanger NHX-2. Since many membrane proteins commonly function as complexes, there could be proteins that possibly modulate PEPT-1 expression and function. A systematic RNAi screening of 162 genes that are exclusively expressed in the intestine combined with a functional transport assay revealed four genes with homologues existing in mammals as predicted PEPT-1 modulators. While silencing of a glutathione peroxidase surprisingly caused an increase in PEPT-1 transport function, silencing of the ER to Golgi cargo transport protein and of two cytosolic peptidases reduced PEPT-1 transport activity and this even corresponded with lower PEPT-1 protein levels. These modifications of PEPT-1 function by gene silencing of homologous genes were also found to be conserved in the human epithelial cell line Caco-2/TC7 cells. Peptidase inhibition, amino acid supplementation and RNAi silencing of targets of rapamycin (TOR) components in C. elegans supports evidence that intracellular peptide hydrolysis and amino acid concentration are a part of a sensing system that controls PEPT-1 expression and function and that involves the TOR complexes TORC1 and TORC2.
authors: ZIEL Research Center of Nutrition and Food Sciences, Abteilung Biochemie, Technische Universität München, Freising, Germany.
authors: Jacqueline
authors: J
authors: Benner
authors: Hannelore
authors: H
authors: Daniel
authors: Britta
authors: B
authors: Spanier
mesh_terms: D000042:Absorption; D000818:Animals; D018938:Caco-2 Cells; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D004151:Dipeptides / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D005979:Glutathione Peroxidase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D042541:Intracellular Space / Q000201:enzymology*; D010447:Peptide Hydrolases / Q000378:metabolism*; D000074011:Peptide Transporter 1; D011401:Promoter Regions, Genetic / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012098:Reproduction / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D004151:Dipeptides; D000074011:Peptide Transporter 1; D012333:RNA, Messenger; D027981:Symporters; D005979:Glutathione Peroxidase; D058570:TOR Serine-Threonine Kinases; D010447:Peptide Hydrolases