Interaction of transmembrane AMPA receptor regulatory proteins with multiple membrane associated guanylate kinases.

Surface expression of AMPA type glutamate receptors requires stargazin or a related transmembrane AMPA receptor regulatory protein (TARP). Furthermore, interaction of the cytosolic tail of TARPs with PDZ domains of PSD-95 targets AMPA receptors to postsynaptic densities. Here, we screened for additional proteins that might interact with the cytosolic domain of TARPs. Screening a rat brain cDNA library with the yeast two-hybrid system yielded six PDZ proteins that can bind tail of TARPs. These PDZ proteins include the four neuronal membrane associated guanylate kinases, PSD-95/SAP-90, PSD-93/Chapsyn-110, SAP-97/hDLG and SAP-102; the multi-PDZ protein, MUPP1; and the mitochondrial PDZ protein, OMP-25. Although all of these proteins can bind to TARPs in vitro, only two of these, PSD-95 and PSD-93 associate with TARPs in brain. We also found that all three PDZ domains from PSD-95 associate with the TARP C-termini with similar affinities. This work identifies biochemical promiscuity for interaction of the TARP C-termini with PDZ domains in vitro, but also shows that only specific synaptic PDZ proteins associate with TARPs in brain.