Uncoupling the Trade-Off between Somatic Proteostasis and Reproduction in Caenorhabditis elegans Models of Polyglutamine Diseases

Frontiers in Molecular Neuroscience
Netta ShemeshAnat Ben-Zvi

Abstract

Caenorhabditis elegans somatic protein homeostasis (proteostasis) is actively remodeled at the onset of reproduction. This proteostatic collapse is regulated cell-nonautonomously by signals from the reproductive system that transmit the commitment to reproduction to somatic cells. Here, we asked whether the link between the reproductive system and somatic proteostasis could be uncoupled by activating downstream effectors in the gonadal longevity cascade. Specifically, we examined whether over-expression of lipl-4 (lipl-4(oe)), a target gene of the gonadal longevity pathway, or increase in arachidonic acid (AA) levels, associated with lipl-4(oe), modulated proteostasis and reproduction. We found that lipl-4(oe) rescued somatic proteostasis and postponed the onset of aggregation and toxicity in C. elegans models of polyglutamine (polyQ) diseases. However, lipl-4(oe) also disrupted fatty acid transport into developing oocytes and reduced reproductive success. In contrast, diet supplementation of AA recapitulated lipl-4(oe)-mediated proteostasis enhancement in wild type animals but did not affect the reproductive system. Thus, the gonadal longevity pathway mediates a trade-off between somatic maintenance and reproduction, in part b...Continue Reading

References

Jul 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·C AmiciR I Morimoto
Mar 15, 1994·Proceedings of the National Academy of Sciences of the United States of America·D A JurivichR I Morimoto
Jan 1, 1997·Human Molecular Genetics·R L Nussbaum, M H Polymeropoulos
Oct 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·J A JohnstonR R Kopito
Jul 18, 2002·Proceedings of the National Academy of Sciences of the United States of America·James F MorleyRichard I Morimoto
Aug 15, 2002·Trends in Genetics : TIG·Huda Y Zoghbi, Juan Botas
Oct 3, 2002·Nature Cell Biology·Soojin KimRichard I Morimoto
Oct 7, 2003·Neuromolecular Medicine·Michael Y Sherman, Paul J Muchowski
Jun 18, 2004·Methods in Molecular Biology·Cindy Voisine, Anne C Hart
Mar 1, 2005·Cell·Thomas B L Kirkwood
Jul 21, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Heather R BrignullRichard I Morimoto
Aug 12, 2006·Science·Ehud CohenAndrew Dillin
Apr 10, 2007·Annual Review of Neuroscience·Harry T Orr, Huda Y Zoghbi
Aug 10, 2007·Nature·Eric J BennettRon R Kopito
Oct 24, 2007·PLoS Genetics·Julide Bilen, Nancy M Bonini
Apr 25, 2008·Proceedings of the National Academy of Sciences of the United States of America·Thomas FlattMarc Tatar
Aug 27, 2009·Proceedings of the National Academy of Sciences of the United States of America·Anat Ben-ZviRichard I Morimoto
Sep 25, 2009·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Jeffrey B MasonJames R Carey
Nov 4, 2009·Cell Metabolism·Eyleen J O'RourkeGary Ruvkun
Nov 10, 2009·Biochemical and Biophysical Research Communications·Makoto Horikawa, Kazuichi Sakamoto
Oct 15, 2010·Nature Reviews. Molecular Cell Biology·Jens TyedmersBernd Bukau
Mar 29, 2011·Cold Spring Harbor Perspectives in Biology·Rebecca C Taylor, Andrew Dillin
Sep 13, 2011·Current Biology : CB·Louis R LapierreMalene Hansen
Oct 16, 2012·Experimental Gerontology·Adam Antebi
Feb 9, 2013·Genes & Development·Eyleen J O'RourkeGary Ruvkun
May 3, 2013·PLoS Genetics·Eric GuisbertRichard I Morimoto
May 21, 2013·FEBS Letters·Gábor BaloghLászló Vígh
Jun 12, 2013·Cell·Patricija van Oosten-HawleRichard I Morimoto
Jun 26, 2013·Cell·Rebecca C Taylor, Andrew Dillin
Aug 9, 2013·Nature Communications·Louis R LapierreMalene Hansen

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Citations

Apr 10, 2019·Cold Spring Harbor Perspectives in Biology·Richard I Morimoto
Sep 25, 2017·Current Genetics·Markus J TamásPierre Goloubinoff
Jul 18, 2019·Cell Reports·Soudabeh ImanikiaRebecca C Taylor
Jan 13, 2021·Experimental Cell Research·Anatoly Meller, Reut Shalgi

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Methods Mentioned

BETA
PCR
protein folding

Software Mentioned

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