Divergent Nodes of Non-Autonomous UPR ER Signaling Through Serotonergic and Dopaminergic Neurons

Autor: Stefan Homentcovschi, Samira Monshietehadi, Naame Kelet, Larry Joe, Jenni Durieux, Andrew Dillin, Sofia Dallarda, Sarah U. Tronnes, Vidhya Ramachandran, Joseph R. Daniele, Gilberto Garcia, Ryo Higuchi-Sanabria
Rok vydání: 2020
Předmět:
Zdroj: SSRN Electronic Journal.
ISSN: 1556-5068
DOI: 10.2139/ssrn.3681991
Popis: In multicellular organisms, neurons integrate a diverse array of external cues to affect downstream changes in organismal health. Specifically, activation of the endoplasmic reticulum (ER) unfolded protein response (UPRER) in neurons increases lifespan by preventing age-onset loss of ER proteostasis and driving lipid depletion in a cell non-autonomous manner. The mechanism of this communication is dependent on release of small clear vesicles from neurons. We find dopaminergic neurons are necessary and sufficient for activation of cell non-autonomous UPRER to drive lipid depletion in peripheral tissues, while serotonergic neurons are necessary and sufficient to drive protein homeostasis in peripheral tissues. These signaling modalities are unique and independent, and together coordinate the benefits of neuronal cell non-autonomous ER stress signaling upon health and longevity.
Databáze: OpenAIRE