Spine-Tingling Excitement from Glutamate Receptors

Ionotropic glutamate receptors excite nerve cells by forming cation-selective pores in the membrane. Recent work, however, provides evidence that atypical signaling by glutamate receptors regulates the production and maintenance of dendritic spines, the short outgrowths that receive most central excitatory synapses. The control of spine formation involves the amino-terminal extracellular domain of the GluR2 subunit of AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptors. How interactions with this domain elicit signals to downstream effectors remains to be elucidated, but ion flux through the channel may not be required. This Perspective discusses the possibility that regulation of spines by GluR2 may be one of a growing collection of cases in which ionotropic glutamate receptors can elicit biochemical changes that are conventionally attributed to metabotropic receptors. It is suggested that proteins in contact with specific glutamate receptor subunits may directly sense the conformational changes produced by agonist binding.