Role of phospholipase D2 in the agonist-induced and constitutive endocytosis of G-protein coupled receptors.
J Neurochem
; 97(2): 365-72, 2006 Apr.
Article
em En
| MEDLINE
| ID: mdl-16539674
ABSTRACT
We have recently shown that the mu-opioid receptor [MOR1, also termed mu-opioid peptide (MOP) receptor] is associated with the phospholipase D2 (PLD2), a phospholipid-specific phosphodiesterase located in the plasma membrane. We further demonstrated that, in human embryonic kidney (HEK) 293 cells co-expressing MOR1 and PLD2, treatment with (D-Ala2, Me Phe4, Glyol5)enkephalin (DAMGO) led to an increase in PLD2 activity and an induction of receptor endocytosis, whereas morphine, which does not induce opioid receptor endocytosis, failed to activate PLD2. In contrast, a C-terminal splice variant of the mu-opioid receptor (MOR1D, also termed MOP(1D)) exhibited robust endocytosis in response to both DAMGO and morphine treatment. We report here that MOR1D also mediates an agonist-independent (constitutive) PLD2-activation facilitating agonist-induced and constitutive receptor endocytosis. Inhibition of PLD2 activity by over-expression of a dominant negative PLD2 (nPLD2) blocked the constitutive PLD2 activation and impaired the endocytosis of MOR1D receptors. Moreover, we provide evidence that the endocytotic trafficking of the delta-opioid receptor [DOR, also termed delta-opioid peptide (DOP) receptor] and cannabinoid receptor isoform 1 (CB1) is also mediated by a PLD2-dependent pathway. These data indicate the generally important role for PLD2 in the regulation of agonist-dependent and agonist-independent G protein-coupled receptor (GPCR) endocytosis.
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Base de dados:
MEDLINE
Assunto principal:
Fosfolipase D
/
Receptores Opioides mu
/
Ala(2)-MePhe(4)-Gly(5)-Encefalina
/
Receptores Acoplados a Proteínas G
/
Endocitose
/
Analgésicos Opioides
Limite:
Humans
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article