Glutamate is the brain’s major excitatory neurotransmitter. Its receptors, which are located in nerve cell membranes, play important roles in synaptic transmission and brain plasticity, and mediate behaviors ranging from learning and memory to voluntary motor activity.
Most glutamate receptors are ion channels and produce signals via electrically charged ions flowing through them. A subtype, GluD2, is not an ion channel. It had been considered an “orphan” receptor with no known function, although loss of the GluD2 gene has been associated with severe ataxia in humans.
Using a technique called single particle electron microscopy (a methodology closely related to cryo-EM), Terunaga Nakagawa, M.D., Ph.D., associate professor of Molecular Physiology and Biophysics in the Vanderbilt University School of Medicine, showed that GluD2 functions through a “molecular bridge” that spans the synapse, or space between nerve cells.
Single particle EM allows researchers to determine the structure of large, flexible membrane-bound receptors in their natural environments in a way that traditional methods cannot, said Nakagawa, a corresponding author of the paper.
While the researchers studied GluD2 in the cerebellum, the part of the brain involved in motor control, Nakagawa said the discovery has implications for understanding excitatory synaptic transmission by other glutamate receptors and in other parts of the brain.