FIGURE 1.

Overview of the relevant interactions within the GluA1/A2/γ·PSD-95·β₂-AR·SAP97·AKAP5/AC/PP2B/PKA complex. AKAP5 (green) recruits PKA and the antagonistic phosphatase PP2B to GluA1 for dynamic phosphorylation and dephosphorylation of Ser-845 (17, 37, 42, 48–50). In detail, a central not completely defined region of AKAP5 interacts with the Src homology 3 (sh3) and guanylate kinase (GK) domains of PSD-95 and SAP97 (blue) (48, 51). SAP97 binds with its first and second PDZ domains to the C terminus of GluA1 (56–58), and PSD-95 binds with its first and second PDZ domains to stargazin (γ2) and its homologues γ3, γ4, and γ8 (collectively depicted as γ), which in turn associate with AMPA receptors (52, 54, 55). The β₂-AR binds with its very C terminus to the third PDZ domain of PSD-95 (5, 6). Various ACs can directly bind with their divergent N termini to AKAP5; AC5 and AC6 but probably not AC2 and AC9 bind to the second of the three polybasic regions (depicted as 1,2,3) in the N terminus of AKAP5 (10–12).