Insulin-like peptides and the mTOR-TFEB pathway protect C. elegans hermaphrodites from Mating-induced Death
- Princeton University, United States
- Stanford University, United States
Abstract
C. elegans lifespan is shortened by mating, but these deleterious effects must be delayed long enough for successful reproduction. Susceptibility to brief mating-induced death is caused by the loss of protection upon self-sperm depletion. Self-sperm maintains the expression of a DAF-2 insulin-like antagonist, INS-37, which promotes the nuclear localization of intestinal HLH-30/TFEB, a key pro-longevity regulator. Mating induces the agonist INS-8, promoting HLH-30 nuclear exit and subsequent death. In opposition to the protective role of HLH-30 and DAF-16/FOXO, TOR/LET-363 and the IIS-regulated Zn-finger transcription factor PQM-1 promote seminal-fluid-induced killing. Self-sperm maintenance of nuclear HLH-30/TFEB allows hermaphrodites to resist mating-induced death until self-sperm are exhausted, increasing the chances that mothers will survive through reproduction. Mothers combat males' hijacking of their IIS pathway by expressing an insulin antagonist that keeps her healthy through the activity of pro-longevity factors, as long as she has her own sperm to utilize.
Data availability
Microarray data are available at the following links:"L4 fog-2(q71) vs N2 hermaphrodites"https://puma.princeton.edu/cgi-bin/exptsets/review.pl?exptset_no=7332"L4 fem-3(q20) vs N2 hermaphrodites"https://puma.princeton.edu/cgi-bin/exptsets/review.pl?exptset_no=7333"D3 mated fog-2(q71) vs pqm-1(ok485) hermaphrodites"https://puma.princeton.edu/cgi-bin/exptsets/review.pl?exptset_no=7334
Article and author information
Author details
Funding
NIH Office of the Director (Pioneer 1DP1OD020400-01)
- Coleen T Murphy
Glenn Foundation for Medical Research (NA)
- Coleen T Murphy
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Shi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Insulin-like peptides and the mTOR-TFEB pathway protect C. elegans hermaphrodites from Mating-induced Death
eLife 8:e46413.
https://doi.org/10.7554/eLife.46413
Further reading
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- Evolutionary Biology
- Genetics and Genomics
Young Caenorhabditis elegans hermaphrodites use their own sperm to protect against the negative consequences of mating.
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- Cell Biology
- Genetics and Genomics
Calcineurin is a highly conserved calcium/calmodulin-dependent serine/threonine protein phosphatase with diverse functions. Inhibition of calcineurin is known to enhance the lifespan of Caenorhabditis elegans through multiple signaling pathways. Aiming to study the role of calcineurin in regulating innate immunity, we discover that calcineurin is required for the rhythmic defecation motor program (DMP) in C. elegans. Calcineurin inhibition leads to defects in the DMP, resulting in intestinal bloating, rapid colonization of the gut by bacteria, and increased susceptibility to bacterial infection. We demonstrate that intestinal bloating caused by calcineurin inhibition mimics the effects of calorie restriction, resulting in enhanced lifespan. The TFEB ortholog, HLH-30, is required for lifespan extension mediated by calcineurin inhibition. Finally, we show that the nuclear hormone receptor, NHR-8, is upregulated by calcineurin inhibition and is necessary for the increased lifespan. Our studies uncover a role for calcineurin in the C. elegans DMP and provide a new mechanism for calcineurin inhibition-mediated longevity extension.
