Chapter 9 Anchoring of glutamate receptors at the synapse

Abstract

Publisher Summary This chapter focuses on the recent progress in the identification of proteins that are involved in clustering and anchoring of glutamate receptors at postsynaptic sites in glutamatergic synapses. The ionotropic glutamate receptors—N-methyl-D-aspartate (NMDA) receptors and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors—are predominantly localized at postsynaptic sites, where they are suitably positioned to bind to the neurotransmitter glutamate released from the presynaptic terminal. Understanding the molecular mechanisms of clustering of glutamate receptors in glutamatergic synapses is important because the correct localization of these receptors is critical for efficient excitatory transmission. Although the key genetic experiments are lacking in mammals, an important genetic finding in drosophila strongly supports the idea that PSD-95 family proteins are involved in synaptic clustering of their ion channel binding partners. The NMDA receptors and AMPA receptors are major classes of ionotropic glutamate receptor. Glutamate also acts on G-protein coupled seven-transmembrane receptors or metabotropic glutamate receptors. Genetic mutations that affect PDZ-containing proteins in invertebrate model organisms result in mislocalization of channels and receptors and cause developmental and behavioral defects.