Glycine triggers a non-ionotropic activity of GluN2A-containing NMDA receptors to confer neuroprotection
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Authors
Hu, Rong
Chen, Juan
Lujan, Brendan J.
Lei, Ruixue
Zhang, Mi
Wang, Zefen
Liao, Mingxia
Li, Zhiqiang
Wan, Yu
Liu, Fang
Issue Date
2016
Type
Article
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Abstract
Ionotropic activation of NMDA receptors (NMDARs) requires agonist glutamate and co-agonist glycine. Here we show that glycine enhances the activation of cell survival-promoting kinase Akt in cultured cortical neurons in which both the channel activity of NMDARs and the glycine receptors are pre-inhibited. The effect of glycine is reduced by shRNA-mediated knockdown of GluN2A subunit-containing NMDARs (GluN2ARs), suggesting that a non-ionotropic activity of GluN2ARs mediates glycine-induced Akt activation. In support of this finding, glycine enhances Akt activation in HEK293 cells over-expressing GluN2ARs. The effect of glycine on Akt activation is sensitive to the antagonist of glycine-GluN1 binding site. As a functional consequence, glycine protects against excitotoxicity-induced neuronal death through the non-ionotropic activity of GluN2ARs and the neuroprotective effect is attenuated by Akt inhibition. Thus, this study reveals an unexpected role of glycine in eliciting a non-ionotropic activity of GluN2ARs to confer neuroprotection via Akt activation.
Description
Citation
Hu, R., Chen, J., Lujan, B., Lei, R., Zhang, M., Wang, Z., É Wan, Q. (2016). Glycine triggers a non-ionotropic activity of GluN2A-containing NMDA receptors to confer neuroprotection. Scientific Reports, 6(1). doi:10.1038/srep34459
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ISSN
2045-2322