Endocannabinoid-Go? signalling inhibits axon regeneration in Caenorhabditis elegans by antagonizing Gq?-PKC-JNK signalling.

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 ?-aminobutyric acid neurons after laser axotomy. Exogenous arachidonoyl ethanolamide inhibits axon regeneration via the Go? subunit GOA-1, which antagonizes the Gq? subunit EGL-30. We further demonstrate that protein kinase C functions downstream of Gq? 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.

SUBMITTER: Pastuhov SI 

PROVIDER: S-EPMC3493645 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature