Role of intracellular loops of cannabinoid CB1 receptor in functional interaction with Gα16

AbstractThe cannabinoid CB1 but not the CB2 receptor was demonstrated to couple via Gα16 to activate phospholipase C after co-expression in COS7 cells. Chimeric CB1/CB2 receptors were used as a model to study receptor–Gα16 interaction. Sequences of the second and third intracellular loops and the carboxy-terminus were substituted from the CB1 into the CB2 receptor. Only the triple mutant with all three regions replaced activated phospholipase C to a similar extent as the CB1 receptor, suggesting that all three intracellular regions are required for interacting with Gα16. Several sub-domains within the third intracellular loop were identified for receptor–Gα16 interaction