Biogenic amine neurotransmitters promote eicosanoid production and protein homeostasis

Kishore K. Joshi, Tarmie L. Matlack, Stephanie Pyonteck, Mehul Vora, Ralph Menzel, Christopher Rongo

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbere51063
JournalEMBO Reports
Volume22
Issue number3
DOIs
StatePublished - Mar 3 2021

All Science Journal Classification (ASJC) codes

  • Genetics
  • Molecular Biology
  • Biochemistry

Keywords

  • dopamine
  • eicosanoid
  • protein homeostasis
  • serotonin
  • ubiquitin

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