Investigating Insulin-like Peptide Signaling-Dependent Stress Resistance in Caenorhabditis Elegans: Possible Modulation Through an Imp-L2-like Binding Protein
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Insulin-like signaling (ILS) regulates metabolism, growth, development and lifespan in both vertebrates and invertebrates. In vertebrates, ILS is triggered not only by insulin but also by insulin-like growth factors (IGFs.) IGF-specific modulation of ILS is partially conferred through IGF-binding proteins (IGFBPs). In Drosophila, ILS is initiated by insulin-like peptides (ILPs) and is also modulated by an IGFBP homolog known as Imp-L2. Specifically, Imp-L2 is upregulated when Drosophila larvae are starved and segregates the ILP in non-signaling complexes. This mechanism prevents ILS-dependent nutrient utilization and prolongs the lifespan of larvae during starvation. Interestingly, the nematode Caenorhabditis elegans, which possesses ILP and ILS, also prolongs its lifespan through decreased metabolism during periods of starvation or other chronic stresses (heat, crowding, etc.). However, it is not known whether ILS in the worm is modulated by an Imp-L2-like protein. To resolve this issue, studies were performed to determine whether an Imp-L2-like protein exists in C. elegans, and whether it prolongs lifespan during periods of stress. Using the Imp-L2 amino acid sequence as a template, the zig-4, zig-3, and zig-2 genes were identified as possible Imp-L2 homologs in C. elegans. Next, RNAi techniques were used to assess the possible roles of the candidate gene products in dauer arrest, lifespan determination, and fat deposition. RNAi against zig-4 significantly lowered dauer arrest frequency in daf-2 mutants compared to the control RNAi (P<0.05), while RNAi against zig-3 and zig-2 had no significant effects on dauer arrest. RNAi against zig-4 also significantly shortened lifespan in wild-type and daf-2 mutants compared to the empty vector control RNAi (P<0.05), but these results were not consistent over several trials. These data are consistent with zig-4 attenuating ILP-dependent ILS and with zig-4 possibly encoding an Imp-L2 homolog in C. elegans.
C. elegans; dauer; Imp-L2; insulin; lifespan
dissertation or thesis