Insulin/insulin-like growth factor signaling in C. elegans

Abstract

The C. elegans insulin/IGF-1 signaling (IIS) pathway connects nutrient levels to metabolism, growth, development, longevity, and behavior. This fundamental pathway is regulated by insulin-like peptide ligands that bind to the insulin/IGF-1 transmembrane receptor (IGFR) ortholog DAF-2. DAF-2/IGFR controls the activity of a conserved phosphoinositide 3-kinase (PI3K)/Akt kinase cascade, culminating in the regulation of a FoxO transcription factor, DAF-16, that governs most of the functions of this pathway. In light of the evolutionary conservation of the IIS pathway, its study in C. elegans is likely to shed light on its functions and regulation in higher organisms, including humans. Originally identified based on its role in the regulation of larval development and aging, IIS also controls a host of other biological processes. Here we review what is currently known about the biological functions and the molecular components of C. elegans IIS.

Ultraviolet-A triggers photoaging in model nematode Caenorhabditis elegans in a DAF-16 dependent pathway

“…DAF-2 is the major player which phosphorylates DAF-16 in cytoplasm and prevents its integration into nucleus. When DAF-2 is mutated, DAF-16 will integrate into the nucleus leading to the activation of many genes responsible for lifespan and stress resistance (Murphy and Hu 2013). The decreased survival in mutant worms due to exposure indicates that this pathway was also affected.…”

“…DAF-2 phosphorylates DAF-16 and prevents it from integrating into nucleus and activating the regulatory genes. Knockdown of DAF-2 allows the activation of DAF-16, and these mutants were known for their extended lifespan (Murphy and Hu 2013;Sonani et al 2014). After exposure, wild type worms survived up to 15, 13, and 14 days in liquid and 15, 15, and 10 days in solid media whereas daf-2 mutants survived up to 40, 35, and 30 days in liquid and 42, 38, and 33 days in solid media, after 2, 4, and 6 h of UVexposure, respectively ( Fig.…”

Sex‐specific regulation of aging in Caenorhabditis elegans

“…Until recently, DAF‐16/FOXO was known to be regulated predominantly at posttranscriptional levels (via phosphorylation by the serine‐threonine kinase Akt; Figure 1b; Murphy & Hu, 2013). TRA‐1 however influenced the transcription of certain daf‐16 isoforms, d/f and a (Figure 2 and 4).…”

Inactivation of GABAA receptor is related to heat shock stress response in organism model Caenorhabditis elegans

“…The expression of the HSP-16.2 small chaperone protein needs joint activity of transcription factors HSF-1 and DAF-16 (Hartwig et al 2009;Hsu et al 2003;Soti and Csermely 2007;Walker and Lithgow 2003;Wiegant et al 2009), both regulated, in turn, by the IIS pathway (Baumeister et al 2006;Chiang et al 2012;Murphy and Hu 2013;Yen et al 2011). This suggests that GABA A inactivation influences the IIS pathway and consequently the stress response.…”