FIGURE 8.

Model summarizing our findings on the role of SAP97 and other scaffolding proteins and kinases on subunit-specific synaptic delivery of AMPARs during early and later stages of in vitro classical conditioning. A, about 15 min after conditioning onset, a SAP97-AKAP/PKA-GluA1 protein complex forms that is initiated by the phosphorylation of PKA. B, shortly after A at about C1 (25 min), this complex translocates to the PSD where there is an interaction between SAP97-PSD95 and GluA1-containing AMPARs are released from SAP97 for delivery to the synapse. C, still later in conditioning at about C2 (80 min after conditioning onset), a SAP97-KSR1/PKC-GluA4 complex forms. This occurs while SAP97 is already bound to PSD95 and/or there are new SAP97 complexes that translocate to the PSD to deliver GluA4 AMPAR subunits to the synapse. This step requires the phosphorylation of ERK. During this phase GluA1-containing AMPARs are removed from the membrane surface.