Molecular organization and regulation of glutamate receptors in developing and adult mammalian central nervous systems

The amino acid glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS), and it exerts its physiological effects by binding to a number of different ionotropic (ligand-gated ion channels) and metabotropic (G-protein-coupled) glutamate receptors. In addition to excitatory neurotransmission, glutamate receptors play an essential role in neuronal differentiation, plastic changes in efficacy of synaptic transmission, neurodegeneration, and neuronal cell death. The application of molecular cloning technology identified a complex and diverse receptor family. To date, 18 different ionotropic glutamate receptor (iGluR) genes and 8 genes for metabotropic glutamate receptors (mGluRs) have been identified from mammals. The availability of more selective drugs, gene knockout mice and high-resolution immunohistochemical studies started to reveal the pharmacological and functional properties of individual iGluR subunits and mGluR isoforms. Wide range of studies in recent years indicated that the activity and synaptic distribution of various glutamate receptors are dynamically regulated by phosphorylation and protein–protein interactions, which are key mechanisms in mediating synaptic plasticity. This chapter reviews some of the recent progress in glutamate receptor research with special emphasis on the molecular diversity of this receptor system and its implications for neuronal development and synaptic plasticity.