RRC ID 76058
Author Shimizu T, Sugiura K, Sakai Y, Dar AR, Butcher RA, Matsumoto K, Hisamoto N.
Title Chemical Signaling Regulates Axon Regeneration via the GPCR-Gqα Pathway in Caenorhabditis elegans.
Journal J Neurosci
Abstract Chemical communication controls a wide range of behaviors via conserved signaling networks. Axon regeneration in response to injury is determined by the interaction between the extracellular environment and intrinsic growth potential. In this study, we investigated the role of chemical signaling in axon regeneration in Caenorhabditis elegans We find that the enzymes involved in ascaroside pheromone biosynthesis, ACOX-1.1, ACOX-1.2, and DAF-22, participate in axon regeneration by producing a dauer-inducing ascaroside, ascr#5. We demonstrate that the chemoreceptor genes, srg-36 and srg-37, which encode G-protein-coupled receptors for ascr#5, are required for adult-specific axon regeneration. Furthermore, the activating mutation in egl-30 encoding Gqα suppresses axon regeneration defective phenotype in acox-1.1 and srg-36 srg-37 mutants. Therefore, the ascaroside signaling system provides a unique example of a signaling molecule that regulates the regenerative pathway in the nervous system.SIGNIFICANCE STATEMENT In Caenorhabditis elegans, axon regeneration is positively regulated by the EGL-30 Gqα-JNK MAP kinase cascade. However, it remains unclear what signals activate the EGL-30 pathway in axon regeneration. Here, we show that SRG-36 and SRG-37 act as upstream G-protein-coupled receptors (GPCRs) that activate EGL-30. C. elegans secretes a family of small-molecule pheromones called ascarosides, which serve various functions in chemical signaling. SRG-36 and SRG-37 are GPCRs for the dauer-inducing ascaroside ascr#5. Consistent with this, we found that ascr#5 activates the axon regeneration pathway via SRG-36/SRG-37 and EGL-30. Thus, ascaroside signaling promotes axon regeneration by activating the GPCR-Gqα pathway.
Volume 42(5)
Pages 720-730
Published 2022-2-2
DOI 10.1523/JNEUROSCI.0929-21.2021
PII JNEUROSCI.0929-21.2021
PMID 34862187
PMC PMC8808735
MeSH Animals Animals, Genetically Modified Axons / physiology* Caenorhabditis elegans Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* GTP-Binding Protein alpha Subunits, Gq-G11 / genetics GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism* Nerve Regeneration / physiology* Receptors, G-Protein-Coupled / genetics Receptors, G-Protein-Coupled / metabolism* Signal Transduction / physiology*
Resource
C.elegans tm7585 tm5192