TRX-1 regulates SKN-1 nuclear localization cell non-autonomously in caenorhabditis elegans

Katie C. McCallum, Bin Liu, Juan Carlos Fierro-González, Peter Swoboda, Swathi Arur, Antonio Miranda-Vizuete, Danielle A. Garsin

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

The Caenorhabditis elegans oxidative stress response transcription factor, SKN-1, is essential for the maintenance of redox homeostasis and is a functional ortholog of the Nrf family of transcription factors. The numerous levels of regulation that govern these transcription factors underscore their importance. Here, we add a thioredoxin, encoded by trx-1, to the expansive list of SKN-1 regulators. We report that loss of trx-1 promotes nuclear localization of intestinal SKN-1 in a redox-independent, cell non-autonomous fashion from the ASJ neurons. Furthermore, this regulation is not general to the thioredoxin family, as two other C. elegans thioredoxins, TRX-2 and TRX-3, do not play a role in this process. Moreover, TRX-1-dependent regulation requires signaling from the p38 MAPK-signaling pathway. However, while TRX-1 regulates SKN-1 nuclear localization, classical SKN-1 transcriptional activity associated with stress response remains largely unaffected. Interestingly, RNA-Seq analysis revealed that loss of trx-1 elicits a general, organism-wide down-regulation of several classes of genes; those encoding for collagens and lipid transport being most prevalent. Together, these results uncover a novel role for a thioredoxin in regulating intestinal SKN-1 nuclear localization in a cell non-autonomous manner, thereby contributing to the understanding of the processes involved in maintaining redox homeostasis throughout an organism.

Original languageEnglish (US)
Pages (from-to)387-402
Number of pages16
JournalGenetics
Volume203
Issue number1
DOIs
StatePublished - May 2016

Keywords

  • ASJ neurons
  • Caenorhabditis elegans
  • Cell non-autonomous signaling
  • Oxidative stress response
  • Thioredoxin

ASJC Scopus subject areas

  • Genetics

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