Coexpressed Auxiliary Subunits Exhibit Distinct Modulatory Profiles on AMPA Receptor Function

Gating properties and surface trafficking of AMPA receptors (AMPARs) are modulated by auxiliary sub-units. Here we studied the function of coexpressed auxiliary subunits belonging to two different classes. We focused on TARP gamma-8 and CKAMP44 in dentate gyrus (DG) granule cells, since both subunits are highly expressed in this cell type. TARP gamma-8 and CKAMP44 decrease the rate of deactivation but have an opposing influence on receptor desensitization, which accounts for their differential modulation of synaptic short-term plasticity. Furthermore, long-term plasticity (LTP) requires TARP gamma-8 but not CKAMP44. The coexpression of both auxiliary subunits is necessary for the efficient targeting of AMPARs to the cell surface of DG granule cells. Finally, electrophysiological and biochemical evidence support the notion that CKAMP44 and TARP gamma-8 can be contained in the same AMPAR complex.