@article{514ccfe2ead84a1aba8b38b747b348aa,
title = "Biogenic amine neurotransmitters promote eicosanoid production and protein homeostasis",
abstract = "Metazoans use protein homeostasis (proteostasis) pathways to respond to adverse physiological conditions, changing environment, and aging. The nervous system regulates proteostasis in different tissues, but the mechanism is not understood. Here, we show that Caenorhabditis elegans employs biogenic amine neurotransmitters to regulate ubiquitin proteasome system (UPS) proteostasis in epithelia. Mutants for biogenic amine synthesis show decreased poly-ubiquitination and turnover of a GFP-based UPS substrate. Using RNA-seq and mass spectrometry, we found that biogenic amines promote eicosanoid production from poly-unsaturated fats (PUFAs) by regulating expression of cytochrome P450 monooxygenases. Mutants for one of these P450s share the same UPS phenotype observed in biogenic amine mutants. The production of n-6 eicosanoids is required for UPS substrate turnover, whereas accumulation of n-6 eicosanoids accelerates turnover. Our results suggest that sensory neurons secrete biogenic amines to modulate lipid signaling, which in turn activates stress response pathways to maintain UPS proteostasis.",
keywords = "dopamine, eicosanoid, protein homeostasis, serotonin, ubiquitin",
author = "Joshi, {Kishore K.} and Matlack, {Tarmie L.} and Stephanie Pyonteck and Mehul Vora and Ralph Menzel and Christopher Rongo",
note = "Funding Information: We thank Matthew Kiel, Tejash Shah, and Iris Tu for their technical assistance in analyzing some of the ubiquitin reporter experiments. We thank A. Fire, the C. elegans Genetics Center, S. Mitani, and the Japanese National Bioresource Project for reagents and strains. We thank Hazel Schubert and Daja O{\textquoteright}Bryant for computational assistance. We thank Eunchan Park and Cathy Savage-Dunn for comments on the manuscript. The manuscript was funded by grants from the National Institutes of Health (R01 NS42023 and R01 GM101972, to CR), as well as the New Jersey Commission on Cancer Research and the Charles and Johanna Busch Fellowship (to KKJ); these agencies had no other role in the research or the manuscript. Funding Information: We thank Matthew Kiel, Tejash Shah, and Iris Tu for their technical assistance in analyzing some of the ubiquitin reporter experiments. We thank A. Fire, the Genetics Center, S. Mitani, and the Japanese National Bioresource Project for reagents and strains. We thank Hazel Schubert and Daja O{\textquoteright}Bryant for computational assistance. We thank Eunchan Park and Cathy Savage‐Dunn for comments on the manuscript. The manuscript was funded by grants from the National Institutes of Health (R01 NS42023 and R01 GM101972, to CR), as well as the New Jersey Commission on Cancer Research and the Charles and Johanna Busch Fellowship (to KKJ); these agencies had no other role in the research or the manuscript. C. elegans Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = mar,
day = "3",
doi = "10.15252/embr.202051063",
language = "English (US)",
volume = "22",
journal = "EMBO Reports",
issn = "1469-221X",
publisher = "Nature Publishing Group",
number = "3",
}