抄録
Memories are thought to be formed and stored as changes in fast neurotransmission mediated by AMPA-type glutamate receptors in the mammalian CNS. Several lines of evidence indicate that changes in the number of AMPA receptors at the postsynaptic sites are one of the major mechanisms underlying such synaptic plasticity. Therefore, a better understanding of molecular mechanisms regulating a life of AMPA receptors in neurons is crucial. An odyssey of AMPA receptors begins when they are synthesized in the endoplasmic reticulum (ER) mostly located in somata of neurons. Interestingly, mutant AMPA receptors that cannot bind to ligands, form channels, or improperly assembled complexes, are actively retained and degraded at the ER by an unknown mechanism. AMPA receptors are then selectively trafficked to dendrites by an adaptor protein complex-4 at the trans-Golgi network (TGN). For the ER exit and TGN sorting processes, transmembrane AMPA receptor regulatory proteins (TARPs) play an indispensable role. AMPA receptors are exocytosed by the vesicle fusion apparatus, such as the exocyst complex, at yet unknown extrasynaptic sites. AMPA receptors then laterally diffuse into synapses, where they are anchored by several proteins including TARPs. AMPA receptors are removed from the synapses by lateral diffusion followed by clathrin-mediated endocytosis at the perisynaptic endocytosis zones. Some AMPA receptors recycle back to the synapses, but others are degraded by a ubiquitin-proteasome system. In this symposium, I would like to introduce recent progresses at each step of the life of AMPA receptors, focusing on our own findings. [J Physiol Sci. 2008;58 Suppl:S26]
