Mutagenesis reveals a role for ABP/GRIP binding to GluR2 in synaptic surface accumulation of the AMPA receptor

We studied the role of PDZ proteins GRIP, ABP, and PICK1 in GluR2 AMPA rece ptor trafficking. An epitope-tagged MycGluR2 subunit, when expressed in hip pocampal cultured neurons, was specifically targeted to the synaptic surfac e. With the mutant MycGluR2 Delta 1-10, which lacks the PDZ binding site, t he overall dendritic intracellular transport and the synaptic surface targe ting were not affected. However, over time, MycGluR2 Delta 1-10 accumulated at synapses significantly less than MycGluR2. Notably, a single residue su bstitution, S880A, which blocks binding to ABP/GRIP but not to PICK1, reduc ed synaptic accumulation to the same extent as the PDZ site truncation. We conclude that the association of GluR2 with ABP and/or GRIP but not PICK1 i s essential for maintaining the synaptic surface accumulation of the recept or, possibly by limiting its endocytotic rate.