| Title: | Chemical Signaling Regulates Axon Regeneration via the GPCR-Gqalpha Pathway in Caenorhabditis elegans |
| Author(s): | Shimizu T; Sugiura K; Sakai Y; Dar AR; Butcher RA; Matsumoto K; Hisamoto N; |
| Address: | "Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya 464-8602, Japan. Department of Chemistry, University of Florida, Gainesville, Florida 32603. Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya 464-8602, Japan g44177a@nucc.cc.nagoya-u.ac.jp i45556a@cc.nagoya-u.ac.jp" |
| DOI: | 10.1523/JNEUROSCI.0929-21.2021 |
| ISSN/ISBN: | 1529-2401 (Electronic) 0270-6474 (Print) 0270-6474 (Linking) |
| 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 Gqalpha 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 Gqalpha-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-Gqalpha pathway" |
| Keywords: | "Animals Animals, Genetically Modified Axons/*physiology Caenorhabditis elegans Caenorhabditis elegans Proteins/genetics/*metabolism GTP-Binding Protein alpha Subunits, Gq-G11/genetics/*metabolism Nerve Regeneration/*physiology Receptors, G-Protein-Coupled;" |
| Notes: | "MedlineShimizu, Tatsuhiro Sugiura, Kayoko Sakai, Yoshiki Dar, Abdul R Butcher, Rebecca A Matsumoto, Kunihiro Hisamoto, Naoki eng R01 GM118775/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural 2021/12/05 J Neurosci. 2022 Feb 2; 42(5):720-730. doi: 10.1523/JNEUROSCI.0929-21.2021. Epub 2021 Dec 3" |
