RRC ID 53281
著者 Joshi KK, Matlack TL, Rongo C.
タイトル Dopamine signaling promotes the xenobiotic stress response and protein homeostasis.
ジャーナル EMBO J
Abstract 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.
巻・号 35(17)
ページ 1885-901
公開日 2016-9-1
DOI 10.15252/embj.201592524
PII embj.201592524
PMID 27261197
PMC PMC5007557
MeSH Animals Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / metabolism Dopamine Agents / metabolism* Dopaminergic Neurons / physiology* Epithelial Cells / drug effects Epithelial Cells / metabolism* Homeostasis* Mechanoreceptors / physiology* Proteins / metabolism* Pseudomonas aeruginosa / immunology Receptors, Dopamine D1 / metabolism Signal Transduction Stress, Physiological
IF 9.889
引用数 6
リソース情報
線虫 tm1392 tm3411