Deletion of the intestinal peptide transporter affects insulin and TOR signaling in Caenorhabditis elegans.
The mammalian intestinal peptide transporter PEPT1 mediates the uptake of di- and tripeptides from the gut lumen into intestinal epithelial cells and acts in parallel with amino acid transporters. Here we address the importance of the PEPT1 orthologue PEP-2 for the assimilation of dietary protein and for overall protein nutrition in Caenorhabditis elegans. pep-2 is expressed specifically along the apical membrane of the intestinal cells, and in pep-2 deletion mutant animals, uptake of intact peptides from the gut lumen is abolished. The consequences are a severely retarded development, reduced progeny and body size, and increased stress tolerance. We show here that pep-2 cross-talks with both the C. elegans target of rapamycin (TOR) and the DAF-2/insulin-signaling pathways. The pep-2 mutant enhances the developmental and longevity phenotypes of daf-2, resulting, among other effects, in a pronounced increase in adult life span. Moreover, all aspects of a weak let-363/TOR RNA interference phenotype are intensified by pep-2 deletion, indicating that pep-2 function upstream of TOR-mediated nutrient sensing. Our findings provide evidence for a predominant role of the intestinal peptide transporter for the delivery of bulk quantities of amino acids for growth and development, which consequently affects signaling pathways that regulate metabolism and aging.
Meissner
Barbara
B
Acolph-Butenandt-Institute/Molecular Neurogenetics, Ludwig-Maximilians-University of Munich, D-80336 Munich, Germany.
Boll
Michael
M
Daniel
Hannelore
H
Baumeister
Ralf
R
D000375:Aging; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism; D017353:Gene Deletion; D005838:Genotype; D007328:Insulin / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008954:Models, Biological; D009154:Mutation; D010455:Peptides / Q000737:chemistry; D010641:Phenotype; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry; D034622:RNA Interference; D015398:Signal Transduction; D013696:Temperature; D013997:Time Factors
D000596:Amino Acids; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D007328:Insulin; D026901:Membrane Transport Proteins; D010455:Peptides; D011506:Proteins; C067802:intestinal peptide-proton cotransporter; D017853:Phosphotransferases (Alcohol Group Acceptor); C472494:let-363 protein, C elegans