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

• Published in: Aging cell 2011-12, Vol.10 (6), p.1021-1031
• Main Authors: Monje, José M., Brokate‐Llanos, Ana M., Pérez‐Jiménez, Mercedes M., Fidalgo, Manuel A., Muñoz, Manuel J.
• Format: Article
• Language: English
• Subjects: Adaptation, Physiological; Animals; Animals, Genetically Modified; C. elegans; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cytochrome P-450 Enzyme System - genetics; Cytochrome P-450 Enzyme System - metabolism; dauer; Gene Expression Regulation - physiology; Genotype; Humans; insulin; Insulin - metabolism; Life Cycle Stages - genetics; longevity; Longevity - genetics; Mutation; nuclear hormone; Phenotype; protein kinase C; Protein Kinase C - genetics; Protein Kinase C - metabolism; Receptor, Insulin - genetics; Receptor, Insulin - metabolism; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - metabolism; Signal Transduction - genetics; Somatomedins - genetics; Somatomedins - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 1474-9718; 1474-9726
• DOI: 10.1111/j.1474-9726.2011.00747.x

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 daf‐9, 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.