In the nervous system, signals are transmitted from cell to cell by the flow of chemical neurotransmitters across a specialized junction known as a synapse. In the vertebrate central nervous system, the major neurotransmitter at excitatory synapses is glutamate, which acts by binding to specific protein receptors expressed on the membrane of the post-synaptic neuron. Although the role of glutamate receptors in transmitting signals is well known, recent work shows that these proteins also contribute to the formation and structure of the synapse itself. In particular, GluD glutamate receptors bind to proteins called neurexins on the presynaptic neuron via a third protein, cerebellin-1. To better understand the importance of this inter-neuronal protein bridge, Basic Sciences investigator Terunaga Nakagawa and colleagues Michisuke Yuzaki (Keio University) and Radu Aricescu (University of Oxford) studied crystal structures of the complex-forming regions of GluD and cerebellin-1. Their results revealed key amino acids in the two proteins that are responsible for the binding interaction, allowing the investigators to test the importance of the interaction in vivo using mice genetically engineered to specifically prevent GluD-cerebellin-1 bridge formation. The results show that the GluD-cerebellin-1 interaction is critical to synapse development in the cerebellum and to the actual proper function of GluD during neurotransmission. This discovery provides important insight into the control of motor coordination in the cerebellum. The work is published in the journal Science [J. Elegheert, et al. (2016), Science, 353, 295].
Image attribution:
Figure reproduced from Wikimedia Commons (author BruceBlaus) under the Creative Commons Attribution-Share Alike 4.0 International license.
