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

33 Pages Posted: 29 Sep 2020 Publication Status: Review Complete

See all articles by Ryo Higuchi-Sanabria

Ryo Higuchi-Sanabria

University of California, Berkeley - Department of Molecular & Cell Biology

Jenni Durieux

University of California, Berkeley - Department of Molecular & Cell Biology

Naame Kelet

University of California, Berkeley - Department of Molecular & Cell Biology

Stefan Homentcovschi

University of California, Berkeley - Department of Molecular & Cell Biology

Samira Monshietehadi

University of California, Berkeley - Department of Molecular & Cell Biology

Gilberto Garcia

University of California, Berkeley - Department of Molecular & Cell Biology

Sofia Dallarda

University of California, Berkeley - Department of Molecular & Cell Biology

Joseph R. Daniele

University of Texas at Houston - TRACTION

Vidhya Ramachandran

University of California, Berkeley - Department of Molecular & Cell Biology

Sarah U. Tronnes

University of Colorado at Boulder - Department of Molecular, Cell, and Developmental Biology

Larry Joe

University of California, Berkeley - Department of Molecular & Cell Biology

Andrew Dillin¹

University of California, Berkeley - Department of Molecular & Cell Biology

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Abstract

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.

Keywords: UPR, serotonin, dopamine, proteostasis, Aging

Suggested Citation

Higuchi-Sanabria, Ryo and Durieux, Jenni and Kelet, Naame and Homentcovschi, Stefan and Monshietehadi, Samira and Garcia, Gilberto and Dallarda, Sofia and Daniele, Joseph R. and Ramachandran, Vidhya and Tronnes, Sarah U. and Joe, Larry and Dillin¹, Andrew, Divergent Nodes of Non-Autonomous UPR ER Signaling Through Serotonergic and Dopaminergic Neurons. Available at SSRN: https://ssrn.com/abstract=3681991 or http://dx.doi.org/10.2139/ssrn.3681991
This version of the paper has not been formally peer reviewed.

Ryo Higuchi-Sanabria

University of California, Berkeley - Department of Molecular & Cell Biology ( email )

142 LSA #3200
Berkeley, CA 94720-3200
United States

Jenni Durieux

University of California, Berkeley - Department of Molecular & Cell Biology ( email )

142 LSA #3200
Berkeley, CA 94720-3200
United States

Naame Kelet

University of California, Berkeley - Department of Molecular & Cell Biology ( email )

142 LSA #3200
Berkeley, CA 94720-3200
United States

Stefan Homentcovschi

University of California, Berkeley - Department of Molecular & Cell Biology ( email )

142 LSA #3200
Berkeley, CA 94720-3200
United States

Samira Monshietehadi

University of California, Berkeley - Department of Molecular & Cell Biology ( email )

142 LSA #3200
Berkeley, CA 94720-3200
United States

Gilberto Garcia

University of California, Berkeley - Department of Molecular & Cell Biology

142 LSA #3200
Berkeley, CA 94720-3200
United States

Sofia Dallarda

University of California, Berkeley - Department of Molecular & Cell Biology ( email )

142 LSA #3200
Berkeley, CA 94720-3200
United States

Joseph R. Daniele

University of Texas at Houston - TRACTION ( email )

Houston, TX 77030
United States

Vidhya Ramachandran

University of California, Berkeley - Department of Molecular & Cell Biology ( email )

142 LSA #3200
Berkeley, CA 94720-3200
United States

Sarah U. Tronnes

University of Colorado at Boulder - Department of Molecular, Cell, and Developmental Biology ( email )

1070 Edinboro Drive
Boulder, CO 80309
United States

Larry Joe

University of California, Berkeley - Department of Molecular & Cell Biology ( email )

142 LSA #3200
Berkeley, CA 94720-3200
United States

Andrew Dillin¹ (Contact Author)

University of California, Berkeley - Department of Molecular & Cell Biology ( email )

142 LSA #3200
Berkeley, CA 94720-3200
United States

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