TY - JOUR
T1 - Tyramine acts downstream of neuronal XBP-1s to coordinate inter-tissue UPRER activation and behavior in C. elegans
AU - Özbey, Neşem P.
AU - Imanikia, Soudabeh
AU - Krueger, Christel
AU - Hardege, Iris
AU - Morud, Julia
AU - Sheng, Ming
AU - Schafer, William R.
AU - Casanueva, M. Olivia
AU - Taylor, Rebecca C.
PY - 2020/12/21
Y1 - 2020/12/21
N2 - 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.
AB - 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.
UR - http://europepmc.org/abstract/med/33232669
U2 - 10.1016/j.devcel.2020.10.024
DO - 10.1016/j.devcel.2020.10.024
M3 - Article
C2 - 33232669
VL - 55
SP - 754-770.e6
JO - Developmental Cell
JF - Developmental Cell
SN - 1534-5807
IS - 6
ER -