Abstract
The proteostasis network is regulated by transcellular communication to promote health and fitness in metazoans. In Caenorhabditis elegans, signals from the germline initiate the decline of proteostasis and repression of cell stress responses at reproductive maturity, indicating that commitment to reproduction is detrimental to somatic health. Here we show that proteostasis and stress resilience are also regulated by embryo-to-mother communication in reproductive adults. To identify genes that act directly in the reproductive system to regulate somatic proteostasis, we performed a tissue targeted genetic screen for germline modifiers of polyglutamine aggregation in muscle cells. We found that inhibiting the formation of the extracellular vitelline layer of the fertilized embryo inside the uterus suppresses aggregation, improves stress resilience in an HSF-1-dependent manner, and restores the heat-shock response in the somatic tissues of the parent. This pathway relies on DAF-16/FOXO activation in vulval tissues to maintain stress resilience in the mother, suggesting that the integrity of the embryo is monitored by the vulva to detect damage and initiate an organismal protective response. Our findings reveal a previously undescribed transcellular pathway that links the integrity of the developing progeny to proteostasis regulation in the parent.
Original language | English (US) |
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Pages (from-to) | 678-687 |
Number of pages | 10 |
Journal | Genes and Development |
Volume | 34 |
Issue number | 9-10 |
DOIs | |
State | Published - May 1 2020 |
Funding
We thank John Labbadia for discussions on the RNAi screening strategy and heat stress assays, Erin Aprison for assistance with germline staining experiments, and Ilya Ruvinsky, Anan Yu, and Thomas Stoeger for critical reading of the manuscript. We also thank the Keck Biophysics and High-Throughput Analysis facilities as well as the laboratory of Robert Lamb at Northwestern University for access to equipment. This work was supported by grants from the National Institutes of Health (National Institute on Aging R56AG059579, R37AG026647, RF1AG057296, and P01AG054407) and the Daniel F. and Ada L. Rice Foundation to R.I.M., and by postdoctoral fellowships from the National Ataxia Foundation and the American Federation for Aging Research as well as a research grant from the Kennedy’s Disease Association to L.C.B.
Keywords
- Embryo
- Heat shock response
- Protein homeostasis
- Stress resistance
- Transcellular regulation
ASJC Scopus subject areas
- Genetics
- Developmental Biology