pkc‐1 regulates daf‐2 insulin/IGF signalling‐dependent control of dauer formation in Caenorhabditis elegans

Summary In Caenorhabditis elegans, the insulin ⁄IGF pathway participates in the decision to initiate dauer development. Dauer is a diapause stage that is triggered by environmental stresses, such as a lack of nutrients. Insulin ⁄IGF receptor mutants arrest constitutively in dauer, an effect that can be suppressed by mutations in other elements of the insulin ⁄IGF pathway or by a reduction in the activity of the nuclear hormone receptor daf-12. We have isolated a pkc-1 mutant that acts as a novel suppressor of the dauer phenotypes caused by insulin ⁄IGF receptor mutations. Interactions between insulin ⁄IGF mutants and the pkc-1 suppressor mutant are similar to those described for daf-12 or the DAF-12 coregulator din-1. Moreover, we show that the expression of the DAF-12 target daf9, which is normally elevated upon a reduction in insulin ⁄IGF receptor activity, is suppressed in a pkc-1 mutant background, suggesting that pkc-1 could link the daf-12 and insulin ⁄IGF pathways. pkc-1 has been implicated in the regulation of peptide neurosecretion in C. elegans. Although we demonstrate that pkc-1 expression in the nervous system regulates dauer formation, our results suggest that the requirement for pkc-1 in neurosecretion is independent of its role in modulating insulin ⁄IGF signalling. pkc-1 belongs to the novel protein kinase C (nPKC) family, members of which have been implicated in insulin resistance and diabetes in mammals, suggesting a conserved role for pkc-1 in the regulation of the insulin ⁄IGF pathway.