P2X-mediated AMPA receptor internalization and synaptic depression is controlled by two CaMKII phosphorylation sites on GluA1 in hippocampal neurons

• DOI: 10.1038/srep31836
• Publication Date: 2016-09-14T08:48:20Z
• Authors: Johan-Till Pougnet; Benjamin Compans; Audrey Martinez; Daniel Choquet; Eric Hosy; Eric Boué-Grabot
• Keywords: Internalization; Long-term depression; Dephosphorylation

Abstract Plasticity at excitatory synapses can be induced either by synaptic release of glutamate or the gliotransmitters such as ATP. Recently, we showed that postsynaptic P2X2 receptors activated ATP released from astrocytes downregulate AMPAR, providing a novel mechanism which glial cells modulate activity. ATP- and lNMDA-induced depression in CA1 region hippocampus are additive, suggesting distinct molecular pathways. AMPARs homo-or hetero-tetramers composed GluA1-A4. Here, first show P2X2-mediated AMPAR inhibition is dependent on subunit composition AMPAR. GluA3 homomers insensitive their presence heteromers alters P2X-mediated inhibition. Using mutational approach, demonstrate two CaMKII phosphorylation sites S567 S831 located cytoplasmic Loop1 C-terminal tail GluA1 subunits, respectively, critical for recorded co-expressing Xenopus oocytes removal surface hippocampal neurons imaged super-resolution dSTORM technique. Finally, using site-specific antibodies, P2X-induced slices produces dephosphorylation S567, contrary to NMDAR-mediated LTD. These findings indicate internalization ATP-driven depression.