Pervasive Positive and Negative Feedback Regulation of Insulin-Like Signaling in Caenorhabditis elegans .
Journal Article (Journal Article)
The Caenorhabditis elegans insulin-like signaling network supports homeostasis and developmental plasticity. The genome encodes 40 insulin-like peptides and one known receptor. Feedback regulation has been reported, but the extent of feedback and its effect on signaling dynamics in response to changes in nutrient availability has not been determined. We measured messenger RNA expression for each insulin-like peptide, the receptor daf-2 , components of the PI3K pathway, and its transcriptional effectors daf-16 /FoxO and skn-1 /Nrf at high temporal resolution during transition from a starved, quiescent state to a fed, growing state in wild type and mutants affecting daf-2 /InsR and daf-16 /FoxO. We also analyzed the effect of temperature on insulin-like gene expression. We found that most PI3K pathway components and insulin-like peptides are affected by signaling activity, revealing pervasive positive and negative feedback regulation at intra- and intercellular levels. Reporter gene analysis demonstrated that the daf-2 /InsR agonist daf-28 positively regulates its own transcription and that the putative agonist ins-6 cross-regulates DAF-28 protein expression through feedback. Our results show that positive and negative feedback regulation of insulin-like signaling is widespread, giving rise to an organismal FoxO-to-FoxO signaling network that supports homeostasis during fluctuations in nutrient availability.
Full Text
Duke Authors
Cited Authors
- Kaplan, REW; Maxwell, CS; Codd, NK; Baugh, LR
Published Date
- January 2019
Published In
Volume / Issue
- 211 / 1
Start / End Page
- 349 - 361
PubMed ID
- 30425043
Pubmed Central ID
- PMC6325697
Electronic International Standard Serial Number (EISSN)
- 1943-2631
International Standard Serial Number (ISSN)
- 0016-6731
Digital Object Identifier (DOI)
- 10.1534/genetics.118.301702
Language
- eng