A critical role for PSD-95/AKAP interactions in endocytosis of synaptic AMPA receptors.

摘要: The endocytosis of AMPA receptors underlies several forms synaptic plasticity. Here, the authors show that PSD-95, via its binding to AKAP150, is important for NMDAR-triggered AMPARS. (AMPARs) plasticity, including NMDA receptor (NMDAR)-dependent long-term depression (LTD), but molecular mechanisms responsible this trafficking remain unknown. We found a major postsynaptic density protein, AMPARs in rat neuron cultures because A kinase–anchoring protein 150 (AKAP150), scaffold specific kinases and phosphatases. Knockdown PSD-95 with shRNA blocked NMDAR-triggered, not constitutive or mGluR-triggered, AMPARs. Deletion PSD-95's Src homology 3 guanylate kinase–like domains, as well point mutation (L460P), both which inhibit also AMPAR endocytosis. Furthermore, expression mutant AKAP150 does bind calcineurin inhibited event. Our results suggest interaction critical LTD, possibly these scaffolds position appropriate subsynaptic domain.