Role of intracellular loops of cannabinoid CB 1 receptor in functional interaction with G α16

• Published in: FEBS letters Vol. 522; no. 1; pp. 130 - 134
• Main Authors: Ho, Begonia Y, Current, Lori, Drewett, James G
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 03.07.2002
• Subjects: Cannabinoid CB 1 receptor; Cannabinoid CB 2 receptor; G protein-coupled receptor; G α16; Mutagenesis; Receptor–G α coupling; G protein-coupled receptor; Mutagenesis; WIN55,212-2, R(+)-[2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrrolol[1,2,3- de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate; CP55,940, (−)-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-4-[3-hydroxypropyl]cyclohexan-1-ol; Receptor–G α coupling; G α16; Cannabinoid CB 2 receptor; Cannabinoid CB 1 receptor
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(02)02917-4

The cannabinoid CB 1 but not the CB 2 receptor was demonstrated to couple via G α16 to activate phospholipase C after co-expression in COS7 cells. Chimeric CB 1/CB 2 receptors were used as a model to study receptor–G α16 interaction. Sequences of the second and third intracellular loops and the carboxy-terminus were substituted from the CB 1 into the CB 2 receptor. Only the triple mutant with all three regions replaced activated phospholipase C to a similar extent as the CB 1 receptor, suggesting that all three intracellular regions are required for interacting with G α16. Several sub-domains within the third intracellular loop were identified for receptor–G α16 interaction.