AMPA-type glutamate receptors (AMPAR) are one of the principal mediators of fast excitatory synaptic transmission in the brain. These receptors associate with multiple integral membrane proteins which influence their trafficking and channel properties. Proline-rich transmembrane protein 1 (PRRT1) is a membrane protein and an understudied component of native AMPAR complexes. In order to understand the regulation of AMPARs by PRRT1, we have performed electrophysiological and biochemical investigations on acute hippocampal slices derived from PRRT1 knockout mice. Our results show that PRRT1 controls the levels of AMPARs at the cell surface, though it is dispensable for synaptic transmission. PRRT1 has differential effects on the stability of AMPAR GluA1 subunit phosphorylated at S845 and at S831, two residues at which the phosphorylation status has major influences on receptor trafficking. Furthermore, PRRT1 is required for NMDA receptor-dependent long-term depression (LTD) and proper NMDA-induced AMPAR trafficking. These findings position PRRT1 as an important regulator of AMPAR stabilization and trafficking in different subcellular pools under basal conditions and during synaptic plasticity.
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