Dopamine signaling promotes the xenobiotic stress response and protein homeostasis.
Multicellular organisms encounter environmental conditions that adversely affect protein homeostasis (proteostasis), including extreme temperatures, toxins, and pathogens. It is unclear how they use sensory signaling to detect adverse conditions and then activate stress response pathways so as to offset potential damage. Here, we show that dopaminergic mechanosensory neurons in C. elegans release the neurohormone dopamine to promote proteostasis in epithelia. Signaling through the DA receptor DOP-1 activates the expression of xenobiotic stress response genes involved in pathogenic resistance and toxin removal, and these genes are required for the removal of unstable proteins in epithelia. Exposure to a bacterial pathogen (Pseudomonas aeruginosa) results in elevated removal of unstable proteins in epithelia, and this enhancement requires DA signaling. In the absence of DA signaling, nematodes show increased sensitivity to pathogenic bacteria and heat-shock stress. Our results suggest that dopaminergic sensory neurons, in addition to slowing down locomotion upon sensing a potential bacterial feeding source, also signal to frontline epithelia to activate the xenobiotic stress response so as to maintain proteostasis and prepare for possible infection.
Department of Genetics, The Waksman Institute Rutgers The State University of New Jersey, Piscataway, NJ, USA.
Kishore K
KK
Joshi
Department of Genetics, The Waksman Institute Rutgers The State University of New Jersey, Piscataway, NJ, USA.
Tarmie L
TL
Matlack
Department of Genetics, The Waksman Institute Rutgers The State University of New Jersey, Piscataway, NJ, USA rongo@waksman.rutgers.edu.
Christopher
0000-0002-1361-5288
C
Rongo
D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D015259:Dopamine Agents / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000502:physiology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006706:Homeostasis; D008465:Mechanoreceptors / Q000502:physiology*; D011506:Proteins / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000276:immunology; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological
D029742:Caenorhabditis elegans Proteins; C488450:Dop-1 protein, C elegans; D015259:Dopamine Agents; D011506:Proteins; D017447:Receptors, Dopamine D1
C. elegans; dopamine; proteostasis; ubiquitin; xenobiotic stress