Tyramine acts downstream of neuronal XBP-1s to coordinate inter-tissue UPRER activation and behavior in C. elegans

Neşem P. Özbey, Soudabeh Imanikia, Christel Krueger, Iris Hardege, Julia Morud, Ming Sheng, William R. Schafer, M. Olivia Casanueva, Rebecca C. Taylor

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In C. elegans, expression of the UPRER transcription factor xbp-1s in neurons cell non-autonomously activates the UPRER in the intestine, leading to enhanced proteostasis and lifespan. To better understand this signaling pathway, we isolated neurons from animals expressing neuronal xbp-1s for transcriptomic analysis, revealing a striking remodeling of transcripts involved in neuronal signaling. We then identified signaling molecules required for cell non-autonomous intestinal UPRER activation, including the biogenic amine tyramine. Expression of xbp-1s in just two pairs of neurons that synthesize tyramine, the RIM and RIC interneurons, induced intestinal UPRER activation and extended longevity, and exposure to stress led to splicing and activation of xbp-1 in these neurons. In addition, we found that neuronal xbp-1s modulates feeding behavior and reproduction, dependent upon tyramine synthesis. XBP-1s therefore remodels neuronal signaling to coordinately modulate intestinal physiology and stress-responsive behavior, functioning as a global regulator of organismal responses to stress.
Original languageEnglish
Pages (from-to)754-770.e6
Number of pages17
JournalDevelopmental Cell
Issue number6
Early online date23 Nov 2020
Publication statusPublished - 21 Dec 2020

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