Intestinal amino acid availability via PEPT-1 affects TORC1/2 signaling and the unfolded protein response.
J Proteome Res
; 13(8): 3685-92, 2014 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-24999909
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Proteínas de Transporte
/
Regulação da Expressão Gênica
/
Transportadores de Cassetes de Ligação de ATP
/
Proteínas de Caenorhabditis elegans
/
Resposta a Proteínas não Dobradas
/
Aminoácidos
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article