Mechanisms of Synaptic Plasticity: From Membrane to Intracellular AMPAR Trafficking

Models for synaptic and intracellular AMPAR trafficking. At synapses, AMPARs (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors) with long cytoplasmic tails (GluR1/2L/4) are retained at nonsynaptic (cytoplasmic) sites and only inserted into synapses after Ras activation, whereas AMPARs with only short cytoplasmic tails (GluR2/3) continuously cycle between synaptic and nonsynaptic sites and they can be removed from the cycling pool after Rap activation. At the ER, AMPARs with long cytoplasmic tails exit from ER rapidly whereas AMPARs with only short cytoplasmic tails are retained in the ER and only exit from ER after Q/R—editing. AMPAR, AMPA receptor; ER, endoplasmic reticulium; LS, lysosome; V/ES, vesicles-endosomes.