Palmitoylation of cysteine 415 of CB1 receptor affects ligand-stimulated internalization and selective interaction with membrane cholesterol and caveolin 1.
Biochim Biophys Acta Mol Cell Biol Lipids
; 1862(5): 523-532, 2017 May.
Article
em En
| MEDLINE
| ID: mdl-28215712
ABSTRACT
We previously demonstrated that CB1 receptor is palmitoylated at cysteine 415, and that such a post-translational modification affects its biological activity. To assess the molecular mechanisms responsible for modulation of CB1 receptor function by S-palmitoylation, in this study biochemical and morphological approaches were paralleled with computational analyses. Molecular dynamics simulations suggested that this acyl chain stabilizes helix 8 as well as the interaction of CB1 receptor with membrane cholesterol. In keeping with these in silico data, experimental results showed that the non-palmitoylated CB1 receptor was unable to interact efficaciously with caveolin 1, independently of its activation state. Moreover, in contrast with the wild-type receptor, the lack of S-palmitoylation in the helix 8 made the mutant CB1 receptor completely irresponsive to agonist-induced effects in terms of both lipid raft partitioning and receptor internalization. Overall, our results support the notion that palmitoylation of cysteine 415 modulates the conformational state of helix 8 and influences the interactions of CB1 receptor with cholesterol and caveolin 1, suggesting that the palmitoyl chain may serve as a functional interface for CB1 receptor localization and function.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Colesterol
/
Ácido Palmítico
/
Receptor CB1 de Canabinoide
/
Caveolina 1
Limite:
Humans
Idioma:
En
Revista:
Biochim Biophys Acta Mol Cell Biol Lipids
Ano de publicação:
2017
Tipo de documento:
Article