title: Intestinal amino acid availability via PEPT-1 affects TORC1/2 signaling and the unfolded protein response.
abstract: The intestinal peptide transporter PEPT-1 plays an important role in development, growth, reproduction, and stress tolerance in Caenorhabditis elegans, as revealed by the severe phenotype of the pept-1-deficient strain. The reduced number of offspring and increased stress resistance were shown to result from changes in the insulin/IGF-signaling cascade. To further elucidate the regulatory network behind the phenotypic alterations in PEPT1-deficient animals, a quantitative proteome analysis combined with transcriptome profiling was applied. Various target genes of XBP-1, the major mediator of the unfolded protein response, were found to be downregulated at the mRNA and protein levels, accompanied by a reduction of spliced xbp-1 mRNA. Proteome analysis also revealed a markedly reduced content of numerous ribosomal proteins. This was associated with a reduction in the protein synthesis rate in pept-1 C. elegans, a process that is strictly regulated by the TOR (target of rapamycine) complex, the cellular sensor for free amino acids. These data argue for a central role of PEPT-1 in cellular amino acid homeostasis. In PEPT-1 deficiency, amino acid levels dropped systematically, leading to alterations in protein synthesis and in the IRE-1/XBP-1 pathway.
authors.affiliation: ZIEL Research Center of Nutrition and Food Sciences, Molecular Nutrition and Biochemistry Unit, Technische Universität München , Gregor-Mendel-Str. 2, 85350 Freising, Germany.
authors.forename: Kerstin E
authors.initials: KE
authors.lastname: Geillinger
authors.forename: Katja
authors.initials: K
authors.lastname: Kuhlmann
authors.forename: Martin
authors.initials: M
authors.lastname: Eisenacher
authors.forename: Pieter
authors.initials: P
authors.lastname: Giesbertz
authors.forename: Helmut E
authors.initials: HE
authors.lastname: Meyer
authors.forename: Hannelore
authors.initials: H
authors.lastname: Daniel
authors.forename: Britta
authors.initials: B
authors.lastname: Spanier
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000596:Amino Acids / Q000032:analysis*; D000818:Animals; D015153:Blotting, Western; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D046912:Multiprotein Complexes / Q000378:metabolism; D040901:Proteomics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D056811:Unfolded Protein Response / Q000235:genetics / Q000502:physiology*
chemical_list: D018528:ATP-Binding Cassette Transporters; D000596:Amino Acids; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D017931:DNA Primers; D046912:Multiprotein Complexes; C548541:XBP-1 protein, C elegans; C113070:pept-1 protein, C elegans; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases