From bedside-to-bench: What disease-associated variants are teaching us about the NMDA receptor.

The Journal of Physiology
Johansen B AminLonnie P Wollmuth

Abstract

NMDA receptors (NMDARs) are glutamate-gated ion channels that contribute to nearly all brain processes. Not surprisingly then, genetic variations in the genes encoding NMDAR subunits can be associated with neurodevelopmental, neurological and psychiatric disorders. These disease-associated variants (DAVs) present challenges, such as defining how DAV-induced alterations in receptor function contribute to disease progression and how to treat the affected individual clinically. As a starting point to overcome these challenges, we need to refine our understanding of the complexity of NMDAR structure function. In this regard, DAVs have expanded our knowledge of NMDARs because they do not just target well-known structure-function motifs, but rather give an unbiased view of structural elements that are important to the biology of NMDARs. Indeed, established NMDAR structure-function motifs have been validated by the appearance of disorders in patients where these motifs have been altered, and DAVs have identified novel structural features in NMDARs such as gating triads and hinges in the gating machinery. Still, the majority of DAVs remain unexplored and occur at sites in the protein with unidentified function or alter receptor propert...Continue Reading

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Citations

Aug 14, 2020·The Journal of Physiology·David Stroebel, Pierre Paoletti
Mar 30, 2020·The Journal of General Physiology·Miranda J McDanielStephen F Traynelis
Jan 16, 2021·The Journal of Physiology·Derek Bowie
Jun 1, 2021·Neuropharmacology·David StroebelPierre Paoletti
Jun 4, 2021·Neuropharmacology·Lonnie P WollmuthLaurent Groc
Jun 16, 2021·Biochemical Pharmacology·R NeffD Bertrand
Jul 25, 2021·Genome Research·Riley E PerszykStephen F Traynelis
Aug 7, 2021·Nature Communications·Meilin TianPierre Paoletti

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