Endocannabinoid-Goα signalling inhibits axon regeneration in Caenorhabditis elegans by antagonizing Gqα-PKC-JNK signalling.
Nat Commun
; 3: 1136, 2012.
Article
en En
| MEDLINE
| ID: mdl-23072806
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Axones
/
Proteínas Tirosina Quinasas
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Caenorhabditis elegans
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Subunidades alfa de la Proteína de Unión al GTP Gi-Go
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Sistema de Señalización de MAP Quinasas
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Proteínas de Caenorhabditis elegans
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Endocannabinoides
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Regeneración Nerviosa
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Japón