Endocannabinoid-Go[alpha] signalling inhibits axon regeneration in Caenorhabditis elegans by antagonizing Gq[alpha]-PKC-JNK signalling

• Published in: Nature communications Vol. 3; p. 1136
• Main Authors: Pastuhov, Strahil Iv, Fujiki, Kota, Nix, Paola, Kanao, Shuka, Bastiani, Michael, Matsumoto, Kunihiro, Hisamoto, Naoki
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.10.2012
• ISSN: 2041-1723
• DOI: 10.1038/ncomms2136

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.