Free RIα is recruited to MVBs by AKAP11. A model for the mechanism of targeting RIα is depicted. AKAP11 binds to the RIα holoenzyme. Upon activation of PKA, AKAP11 stays bound to RIα, which is recruited to multivesicular bodies (MVBs). If the RIα holoenzyme is not activated, as in the case of RIα(R211K):PKAc, RIα does not get targeted. Likewise, free RIα is not targeted properly when AKAP11 binding is disrupted, as in the case with the RIα(I27A) mutation or in the presence of RI-selective AKAP disruptors. R, RIa; C, PKAc; wt, wild type.