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How an activation signal is transmitted through an excitatory receptor

Glutamate receptors facilitate the transmission of excitatory signals in the brain. A series of structures reveals how the shape of one such receptor alters on activation, providing insight that might aid drug discovery.
  1. Karen J. Gregory

    1. Karen J. Gregory is in Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, and in the Department of Pharmacology, Monash University, Parkville, Victoria 3052, Australia.

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Glutamate is the main neurotransmitter molecule in the brain responsible for communicating excitatory signals between brain cells. This communication is mediated through glutamate-activated receptor proteins embedded in the membranes of brain cells. One of these receptors, metabotropic glutamate receptor 5 (mGlu5), is crucial for learning and memory, and is an attractive target for the treatment of several psychiatric and neurological disorders. Writing in Nature, Koehl et al.1 report the first essentially full-length structures of mGlu5, which they obtained by using a combination of X-ray crystallography and cryo-electron microscopy (cryo-EM). These structures reveal how activation of the receptor alters its multidomain structure to initiate cell signalling.

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Nature 566, 42-43 (2019)

doi: https://doi.org/10.1038/d41586-018-07885-x

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