RRC ID 18750
Author Pastuhov SI, Fujiki K, Nix P, Kanao S, Bastiani M, Matsumoto K, Hisamoto N.
Title Endocannabinoid-Goα signalling inhibits axon regeneration in Caenorhabditis elegans by antagonizing Gqα-PKC-JNK signalling.
Journal Nat Commun
Abstract The ability of neurons to regenerate their axons after injury is determined by a balance between cellular pathways that promote and those that inhibit regeneration. In Caenorhabditis elegans, axon regeneration is positively regulated by the c-Jun N-terminal kinase mitogen activated protein kinase pathway, which is activated by growth factor-receptor tyrosine kinase signalling. Here we show that fatty acid amide hydrolase-1, an enzyme involved in the degradation of the endocannabinoid anandamide (arachidonoyl ethanolamide), regulates the axon regeneration response of γ-aminobutyric acid neurons after laser axotomy. Exogenous arachidonoyl ethanolamide inhibits axon regeneration via the Goα subunit GOA-1, which antagonizes the Gqα subunit EGL-30. We further demonstrate that protein kinase C functions downstream of Gqα and activates the MLK-1-MEK-1-KGB-1 c-Jun N-terminal kinase pathway by phosphorylating MLK-1. Our results show that arachidonoyl ethanolamide induction of a G protein signal transduction pathway has a role in the inhibition of post-development axon regeneration.
Volume 3
Pages 1136
Published 2012
DOI 10.1038/ncomms2136
PII ncomms2136
PMID 23072806
PMC PMC3493645
MeSH Amidohydrolases / metabolism Amino Acid Sequence Animals Arachidonic Acids / metabolism Axons / physiology* Caenorhabditis elegans / enzymology* Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / antagonists & inhibitors Caenorhabditis elegans Proteins / metabolism* Endocannabinoids / metabolism* GTP-Binding Protein alpha Subunits, Gi-Go / metabolism* GTP-Binding Protein alpha Subunits, Gq-G11 / antagonists & inhibitors GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism Genes, Helminth / genetics JNK Mitogen-Activated Protein Kinases / metabolism MAP Kinase Kinase Kinases / chemistry MAP Kinase Kinase Kinases / metabolism MAP Kinase Signaling System* Models, Biological Molecular Sequence Data Nerve Regeneration / physiology* Polyunsaturated Alkamides / metabolism Protein-Tyrosine Kinases / metabolism*
IF 12.353
Times Cited 17
C.elegans tm5011 tm737