Premium
Regulation of CB 1 cannabinoid receptor trafficking by the adaptor protein AP‐3
Author(s) -
Rozenfeld Raphael,
Devi Lakshmi A.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.07-102731
Subject(s) - microbiology and biotechnology , receptor , endocytic cycle , signal transducing adaptor protein , endosome , intracellular , gpr18 , g protein coupled receptor , endocytosis , heterotrimeric g protein , immune receptor , rhodopsin like receptors , g protein , signal transduction , biology , chemistry , cannabinoid receptor , biochemistry , glutamate receptor , metabotropic receptor , agonist
Cannabinoid receptor 1 (CB 1 ) is an abundant G protein‐coupled receptor, involved in a number of physiological processes. This receptor is localized at the plasma membrane, as well as in intra cellular vesicles. The trafficking events leading to this intracellular localization remain controversial. In this study, we examine the differential trafficking of CB 1 receptors and its implication on signaling. We find that the transfected tagged receptors are predominantly at the plasma membrane, whereas endogenous receptors exhibit an intracellular localization. We also find that intracellular endogenous CB 1 receptors do not have an endocytic origin. Instead, these receptors associate with the adaptor protein AP‐3 and traffic to the lysosomes. siRNA‐mediated AP‐3δ knockdown leads to enhanced cell surface localization of CB 1 receptors. Finally, we show that CB 1 receptors in the late endosomal/lysosomal compartment are associated with heterotrimeric G proteins and mediate signal transduction. These results suggest that intracellular CB 1 receptors are functional and that their spatial segregation is likely to significantly affect receptor function.—Rozenfeld, R., Devi, L. A. Regulation of CB 1 cannabinoid receptor trafficking by the adaptor protein AP‐3. FASEB J. 22, 2311–2322 (2008)