Distinct mechanisms of non-autonomous UPR ER mediated by GABAergic, glutamatergic, and octopaminergic neurons.

Autor:	Coakley AJ; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, United States., Hruby A; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, United States., Wang J; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, United States., Bong A; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, United States., Nair T; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, United States., Ramos CM; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, United States., Alcala A; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, United States., Averbukh M; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, United States., Dutta N; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, United States., Moaddeli D; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, United States., Hicks D; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, United States., de Los Rios Rogers M; Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, CA 90095, United States., Sahay A; Department of Cell & Molecular Biology, University of Pennsylvania, Philadelphia, PA 19104, United States., Curran SP; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, United States., Mullen PJ; Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, United States., Benayoun BA; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, United States.; Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, CA 90095, United States.; Department of Cell & Molecular Biology, University of Pennsylvania, Philadelphia, PA 19104, United States.; Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, United States., Garcia G; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, United States., Higuchi-Sanabria R; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, United States.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 May 30. Date of Electronic Publication: 2024 May 30.
DOI:	10.1101/2024.05.27.595950
Abstrakt:	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 (UPR ER ) 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 UPR ER by overexpression of the major transcription factor, xbp-1s , solely in neurons drives lifespan extension as neurons send a neurotransmitter-based signal to other tissue to activate UPR ER in a non-autonomous fashion. Previous work identified serotonergic and dopaminergic 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 UPR ER solely in glutamatergic, octopaminergic, and GABAergic neurons in C. elegans and paired whole-body transcriptomic analysis with functional assays. We found that UPR ER -induced signals from glutamatergic neurons increased expression of canonical protein homeostasis pathways and octopaminergic neurons promoted pathogen response pathways, while minor, but statistically significant changes were observed in lipid metabolism-related genes with GABAergic UPR ER activation. These findings provide further evidence for the distinct role neuronal subtypes play in driving the diverse response to ER stress. Competing Interests: Competing Financial Interests All authors of the manuscript declare that they have no competing interests.
Databáze:	MEDLINE
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