Intestinal amino acid availability via PEPT-1 affects TORC1/2 signaling and the unfolded protein response

Kerstin E. Geillinger, Katja Kuhlmann, Martin Eisenacher, Pieter Giesbertz, Helmut E. Meyer, Hannelore Daniel, Britta Spanier

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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.

Original languageEnglish
Pages (from-to)3685-3692
Number of pages8
JournalJournal of Proteome Research
Volume13
Issue number8
DOIs
StatePublished - 1 Aug 2014

Keywords

  • Caenorhabditis elegans
  • PEPT-1
  • TOR
  • XBP-1
  • unfolded protein response

Fingerprint

Dive into the research topics of 'Intestinal amino acid availability via PEPT-1 affects TORC1/2 signaling and the unfolded protein response'. Together they form a unique fingerprint.

Cite this