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

Kerstin E Geillinger1, Katja Kuhlmann, Martin Eisenacher

  • 1ZIEL Research Center of Nutrition and Food Sciences, Molecular Nutrition and Biochemistry Unit, Technische Universität München , Gregor-Mendel-Str. 2, 85350 Freising, Germany.

Journal of Proteome Research
|July 8, 2014
PubMed

Insights

The intestinal peptide transporter PEPT-1 is crucial for C. elegans development and stress response. Its deficiency disrupts amino acid homeostasis, impacting protein synthesis and the XBP-1 pathway.

Area of Science:

  • Molecular Biology
  • Genetics
  • Physiology

Background:

  • The intestinal peptide transporter PEPT-1 is vital for development, growth, reproduction, and stress tolerance in C. elegans.
  • PEPT-1 deficiency leads to severe phenotypes, including reduced offspring and enhanced stress resistance, linked to the insulin/IGF-signaling cascade.

Purpose of the Study:

  • To investigate the regulatory network underlying phenotypic alterations in PEPT-1-deficient C. elegans.
  • To elucidate the role of PEPT-1 in cellular amino acid homeostasis and its connection to protein synthesis and stress response pathways.

Main Methods:

  • Quantitative proteome analysis
  • Transcriptome profiling
  • Analysis of spliced xbp-1 mRNA levels
  • Measurement of protein synthesis rates

Main Results:

  • Downregulation of XBP-1 target genes at both mRNA and protein levels in PEPT-1 deficient worms.
  • Reduced content of ribosomal proteins and a decreased protein synthesis rate.
  • Systematic drop in amino acid levels in PEPT-1 deficient C. elegans.

Conclusions:

  • PEPT-1 plays a central role in maintaining cellular amino acid homeostasis.
  • PEPT-1 deficiency disrupts protein synthesis via the TOR complex and affects the IRE-1/XBP-1 pathway.
  • These disruptions contribute to the observed developmental and stress tolerance phenotypes in C. elegans.

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