pkc‐1regulatesdaf‐2insulin/IGF signalling‐dependent control of dauer formation inCaenorhabditis elegans

Abstract

SummaryIn 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.

Multilayered Reprogramming in Response to Persistent DNA Damage in C. elegans

“…Although IP3 promotes calcium release (Ca 2+ ), DAG is an intermediate of the glycerophospholipids synthesis ( Figure 4 ) and functions as a cofactor for the activation of PKC. The cluster of proteins downstream of PKC have been implicated in the regulation of daf-2 IIS-dependent control of dauer formation ( Monje et al., 2011 ) and in the secretion of synaptic vesicles at motor neurons ( Sieburth et al., 2007 ). Consistently, we detected a high abundance of the downstream components of the G protein signaling, involved in the neuronal synaptic machinery, and mediating the initial vesicles assembly ( Figures 1 D, 5 , and 6 A; Table 1 ).…”

Nuclear receptor signal transduction in C. elegans

“…Moderate thermal stress, pheromone level, or modest downregulation of TGF-β, IIS, or steroidal signaling, also visibly upregulate hypodermal daf-9, presumably increasing DA to sustain reproductive development. Factors required for this upregulation include daf-12, as well as ttx-1, tax-2, pkc-1, and hsf-1 genes functioning in thermotaxis neurons, revealing a complex regulatory network linked to temperature cues (Lee and Kenyon, 2009;Monje et al, 2011;Barna et al, 2012). In unfavorable dauer inducing conditions, DA production falls below a threshold, hypodermal amplification is suppressed, and animals undergo dauer development.…”

Co-chaperone p23 Regulates C. elegans Lifespan in Response to Temperature

“…We also examined thermotaxis mutants ( pkc-1 , ttx-3 ) that modulate dauer formation dependent on temperature and signaling pathway (e.g. ttx-3 suppresses daf-7 /TGF-β Daf-c phenotype at 25°C, but enhances it at 15°C) [ 43 , 44 ].…”