Lectins modulate the functional properties of GluN1/GluN3-containing NMDA receptors

0508566 - FGÚ 2020 RIV NL eng J - Journal Article
Hemelíková, Katarína - Kolcheva, Marharyta - Skřenková, Kristýna - Kaniaková, Martina - Horák, Martin
Lectins modulate the functional properties of GluN1/GluN3-containing NMDA receptors.
Neuropharmacology. Roč. 157, Oct (2019), č. článku UNSP 107671. ISSN 0028-3908. E-ISSN 1873-7064
R&D Projects: GA ČR(CZ) GA18-04329S
Institutional support: RVO:67985823
Keywords : glycosylation * glutamate receptor * ion channel * patch-clamp technique * desensitization * posttranslational modification
OECD category: Neurosciences (including psychophysiology
Impact factor: 4.431, year: 2019
Method of publishing: Limited access
https://doi.org/10.1016/j.neuropharm.2019.107671

N-methyl-d-aspartate receptors (NMDARs) play an essential role in excitatory neurotransmission within the mammalian central nervous system (CNS). NMDARs are heteromultimers containing GluN1, GluN2, and/or GluN3 subunits, thus giving rise to a wide variety of subunit combinations, each with unique functional and pharmacological properties. Importantly, GluN1/GluN3A and GluN1/GluN3B receptors form glycine-gated receptors. Here, we combined electrophysiology with rapid solution exchange in order to determine whether the presence of specific N-glycans and/or interactions with specific lectins regulates the functional properties of GluN1/GluN3A and GluN1/GluN3B receptors expressed in human embryonic kidney 293 (HEK293) cells. We found that removing putative N-glycosylation sites alters the functional properties of GluN1/GluN3B receptors, but has no effect on GluN1/GluN3A receptors. Moreover, we found that the functional properties of both GluN1/GluN3A and GluN1/GluN3B receptors are modulated by a variety of lectins, including Concanavalin A (ConA), Wheat Germ Agglutinin (WGA), and Aleuria Aurantia Lectin (AAL), and this effect is likely mediated by a reduction in GluN1 subunit-mediated desensitization. We also found that AAL has the most profound effect on GluN1/GluN3 receptors, and this effect is mediated partly by a single N-glycosylation site on the GluN3 subunit (specifically, N565 on GluN3A and N465 on GluN3B). Finally, we found that lectins mediate their effect only when applied to non-activated receptors and have no effect when applied in the continuous presence of glycine. These findings provide further evidence to distinguish GluN1/GluN3 receptors from the canonical GluN1/GluN2 receptors and offer insight into how GluN1/GluN3 receptors may be regulated in the mammalian CNS.
Permanent Link: http://hdl.handle.net/11104/0299434