Multi-level control of ionotropic glutamate receptor function.

Because ionotropic glutamate receptors play critical roles in numerous CNS functions, there has been considerable interest in understanding molecular mechanisms regulating their properties. In particular, the search for ligands and corresponding binding sites providing allosteric regulation of agonist binding and channel opening and closing has been intensely pursued in the hope of developing new approaches for the treatment of a variety of CNS diseases associated with abnormal functioning of glutamatergic systems. Several recent publications have reported detailed structures of the N-terminal domains of NMDA and AMPA receptors and have generated interesting predictions regarding the possibility of finding new ways to control glutamate receptor function. Together with the recently reported control of the receptors by transmembrane proteins, there is now a whole set of potential regulators of these important families of receptors.