Citation | Geillinger KE, Kuhlmann K, Eisenacher M, Giesbertz P, Meyer HE, Daniel H, Spanier B. Intestinal amino acid availability via PEPT-1 affects TORC1/2 signaling and the unfolded protein response. J Proteome Res, 2014. |
PubMed ID | 24999909 |
Short Description | Intestinal amino acid availability via PEPT-1 affects TORC1/2 signaling and the unfolded protein response. GEO Record: N.A. Platform: N.A. Download gene-centric, log2 transformed data: WBPaper00045460.ce.ms.csv |
# of Conditions | 14 |
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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. Experimental Details: MassSpec_WBPaper00045460:N2_20h_after_L1_rep1 MassSpec_WBPaper00045460:N2_40h_after_L1_rep1 MassSpec_WBPaper00045460:N2_60h_after_L1_rep1 MassSpec_WBPaper00045460:N2_20h_after_L1_rep2 MassSpec_WBPaper00045460:N2_40h_after_L1_rep2 MassSpec_WBPaper00045460:N2_60h_after_L1_rep2 MassSpec_WBPaper00045460:pept-1(lg601)_20h_after_L1_rep1 MassSpec_WBPaper00045460:pept-1(lg601)_20h_after_L1_rep2 MassSpec_WBPaper00045460:pept-1(lg601)_40h_after_L1_rep1 MassSpec_WBPaper00045460:pept-1(lg601)_40h_after_L1_rep2 MassSpec_WBPaper00045460:pept-1(lg601)_60h_after_L1_rep1 MassSpec_WBPaper00045460:pept-1(lg601)_60h_after_L1_rep2 MassSpec_WBPaper00045460:pept-1(lg601)_80h_after_L1_rep1 MassSpec_WBPaper00045460:pept-1(lg601)_80h_after_L1_rep2. |
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