Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family.
By S. Pierce, Michael A. Costa, R. Wisotzkey, Sharmila Devadhar, Sheila A. Homburger, A. R. Buchman, K. Ferguson, Jonathan D. Heller, D. Platt, Amy A. Pasquinelli and 3 more. Genes & Development, 2001
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The activity of the DAF-2 insulin-like receptor is required for Caenorhabditis elegans reproductive growth and normal adult life span. Informatic analysis identified 37 C. elegans genes predicted to encode insulin-like peptides. Many of these genes are divergent insulin superfamily members, and many are clustered, indicating recent diversification of the family. The ins genes are primarily expressed in neurons, including sensory neurons, a subset of which are required for reproductive development. Structural predictions and likely C-peptide cleavage sites typical of mammalian insulins suggest that ins-1 is most closely related to insulin. Overexpression of ins-1, or expression of human insulin under the control of ins-1 regulatory sequences, causes partially penetrant arrest at the dauer stage and enhances dauer arrest in weak daf-2 mutants, suggesting that INS-1 and human insulin antagonize DAF-2 insulin-like signaling. A deletion of the ins-1 coding region does not enhance or suppress dauer arrest, indicating a functional redundancy among the 37 ins genes. Of five other ins genes tested, the only other one bearing a predicted C peptide also antagonizes daf-2 signaling, whereas four ins genes without a C peptide do not, indicating functional diversity within the ins family.
Subfields: Aging, Endocrine and Autonomic Systems, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/226bffbead3c2011438bbdacfab33d16f19f4b11
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Citations in the corpus
- Insulin signaling promotes germline proliferation in C. elegans (2010, methodology): “, 1997), and 40 putative insulinlike peptide genes (Pierce et al., 2001).”
- PI3K/Akt: getting it right matters (2008, background): “…a gene encoding a structural homolog of PTEN; age-1, a gene encoding a PI3K homolog; pdk-1, a gene encoding a PDK1 homolog; and other upstream components encoded by the insulin-like (ins-1) and insulin/IGF1 receptor (daf-2) genes (Ogg and Ruvkun, 1998; Paradis et al., 1999; Pierce et al., 2001).”
- Chemosensation in C. elegans. (2006, background): “The chemosensory neurons express numerous secreted peptides of the TGF beta family, the insulin family and neuropeptide families (Li et al., 1999; Li et al., 2003; Nathoo et al., 2001; Pierce et al., 2001; Ren et al., 1996; Schackwitz et al., 1996).”