Desensitizing interactions

The strength of synaptic responses is controlled by neurotransmitter receptor activation, deactivation, and desensitization. The structural basis of desensitization has not been well understood, but Yu Sun, Rich Olson, Eric Gouaux (Columbia University, New York, NY), and colleagues are getting a look at how subunit interactions determine whether glutamate receptors are activated or desensitized.

AMPA-sensitive glutamate receptors can either be activated or desensitized upon glutamate binding. Desensitization, in which the receptor is bound to ligand but inactive, allows for rapid cessation of signaling in the presence of agonist. AMPA receptors are arranged as heterotetramers, but Gouaux's group has determined that the functionally relevant structure for the ligand-binding core for desensitization is that of dimers of dimers.

Using crystallographic and functional analyses of site-directed mutant subunits of GluR2, they show that the stability of the...