| Title: |
Distinct responses to non-autonomous UPRER mediated by glutamatergic and octopaminergic neurons |
| Authors: |
Aeowynn J. Coakley; Adam J. Hruby; Jing Wang; Andrew Bong; Tripti Nair; Carmen M. Ramos; Athena Alcala; Daniel Hicks; Maxim Averbukh; Naibedya Dutta; Darius Moaddeli; Camilla Pearson; Cynthia J. Siebrand; Mattias de los Rios Rogers; Arushi Sahay; Sean P. Curran; Peter J. Mullen; Bérénice A. Benayoun; Gilberto Garcia; Ryo Higuchi-Sanabria |
| Source: |
Communications Biology, Vol 8, Iss 1, Pp 1-19 (2025) |
| Publisher Information: |
Nature Portfolio |
| Publication Year: |
2025 |
| Collection: |
Directory of Open Access Journals: DOAJ Articles |
| Subject Terms: |
Biology (General); QH301-705.5 |
| Description: |
The capacity to deal with stress declines during the aging process, and preservation of cellular stress responses is critical to healthy aging. The unfolded protein response of the endoplasmic reticulum (UPRER) is one such conserved mechanism, which is critical for the maintenance of several major functions of the ER during stress, including protein folding and lipid metabolism. Hyperactivation of the UPRER by overexpression of the major transcription factor, xbp-1s, solely in neurons drives lifespan extension as neurons send a neurotransmitter-based signal to other tissues to activate UPRER in a non-autonomous fashion. Previous work identified serotonergic, dopaminergic, and tyraminergic neurons in this signaling paradigm. To further expand our understanding of the neural circuitry that underlies the non-autonomous signaling of ER stress, we activated UPRER solely in glutamatergic, octopaminergic, and GABAergic neurons in C. elegans and paired whole-body transcriptomic analysis with functional assays. We found that UPRER-induced signals from glutamatergic neurons increased expression of canonical protein homeostasis pathways and octopaminergic neurons promoted pathogen response pathways, while more modest changes were detected in GABAergic UPRER activation. These findings provide further evidence for the distinct role neuronal subtypes play in driving the diverse response to ER stress. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://doi.org/10.1038/s42003-025-09036-1; https://doaj.org/toc/2399-3642; https://doaj.org/article/b39d4128831648149aaab77b933f866f |
| DOI: |
10.1038/s42003-025-09036-1 |
| Availability: |
https://doi.org/10.1038/s42003-025-09036-1; https://doaj.org/article/b39d4128831648149aaab77b933f866f |
| Accession Number: |
edsbas.C019532E |
| Database: |
BASE |