DOI: 10.1101/471755Nov 16, 2018Paper

SKN-1/Nrf2 regulation of neuromuscular function in response to oxidative stress requires EGL-15/FGF Receptor and DAF-2/insulin Receptor signaling in Caenorhabditis elegans.

BioRxiv : the Preprint Server for Biology
Sungjin Kim, Derek Sieburth

Abstract

The transcription factor Nrf2 plays a critical role in the organism wide-regulation of the antioxidant stress response. The Nrf2 homolog SKN-1 functions in the intestine cell non-autonomously to negatively regulate neuromuscular (NMJ) function in Caenorhabditis elegans . To identify additional molecules that mediate SKN-1 signaling to the NMJ, we performed a candidate screen for suppressors of aldicarb-resistance caused by acute treatment with the SKN-1 activator, arsenite. We identified two receptor tyrosine kinases, EGL-15 (fibroblast growth factor receptor, FGFR) and DAF-2 (insulin-like peptide receptor, IR) that are required for NMJ regulation in response to stress. Through double mutant analysis, we found that EGL-15 functions downstream of SKN-1 and SPHK-1 (sphingosine kinase), and that the EGL-15 ligand EGL-17 FGF and canonical EGL-15 effectors are required for oxidative stress-mediated regulation of NMJ function. DAF-2 also functions downstream of SKN-1, independently of DAF-16/FOXO, to regulate NMJ function. Through tissue-specific rescue experiments, we found that FGFR signaling functions primarily in the hypodermis, whereas IR signaling is required in multiple tissues. Our results support the idea that the regulation...Continue Reading

Related Concepts

Insulin Receptor
Signal Transduction
Somatomedins
Arsenite
Fibroblast Growth Factor Receptors
Sphingosine kinase
Antigens, CD55
Caenorhabditis elegans
Receptor Protein-Tyrosine Kinases
Fibroblast Growth Factor Receptor 2

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