FIGURE 10.
Working model for spinophilin- and PKA-dependent β to α2AAR cross-talk modulating endogenous α2AAR endocytosis. A, when α2AARs are activated alone, the spinophilin regulatory mechanism will be fully engaged, and α2AAR responsiveness will be determined by interplay between spinophilin and arrestin binding to the receptor. Relative to co-activating conditions, there would be a net effect of decreased arrestin binding and decreased rate of agonist-stimulated α2AAR endocytosis. B, under β and α2AAR co-activating conditions, canonical βAR/Gαs signal transduction coupled to PKA activation will result in PKA-dependent phosphorylation of spinophilin. This phosphorylation attenuates the ability of spinophilin to interact with α2AARs, which would lead to a predominance of arrestin binding and a net effect of increased rate of agonist-stimulated α2AAR endocytosis.