| 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 |
2012-1-1
|
| 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 |
12.121
|
| Times Cited |
30
|
|
WOS Category
|
NEUROSCIENCES
|
| Resource |
| C.elegans |
tm5011
tm737 |
