Glutamate Receptor

Molnár, Elek

doi:10.1007/978-3-319-67199-4_304

Cited by 3 publications

(3 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Kainate receptors (KARs) are members of the ionotropic glutamate receptor (iGluR) family [ 1 , 2 ]. Presynaptically KARs modulate neurotransmitter (glutamate, GABA) release, postsynaptically they contribute to the slow component of excitatory postsynaptic current (EPSC), thereby influencing neuronal excitability and network dynamics [ 1 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

Assembly and Trafficking of Homomeric and Heteromeric Kainate Receptors with Impaired Ligand Binding Sites

et al. 2018

Self Cite

View full text Add to dashboard Cite

Kainate receptors (KARs) are a subfamily of ionotropic glutamate receptors (iGluRs) mediating excitatory synaptic transmission. Cell surface expressed KARs modulate the excitability of neuronal networks. The transfer of iGluRs from the endoplasmic reticulum (ER) to the cell surface requires occupation of the agonist binding sites. Here we used molecular modelling to produce a range of ligand binding domain (LBD) point mutants of GluK1–3 KAR subunits with and without altered agonist efficacy to further investigate the role of glutamate binding in surface trafficking and activation of homomeric and heteromeric KARs using endoglycosidase digestion, cell surface biotinylation and imaging of changes in intracellular Ca2+ concentration [Ca2+]i. Mutations of conserved amino acid residues in the LBD that disrupt agonist binding to GluK1–3 (GluK1-T675V, GluK2-A487L, GluK2-T659V and GluK3-T661V) reduced both the total expression levels and cell surface delivery of all of these mutant subunits compared to the corresponding wild type in transiently transfected human embryonic kidney 293 (HEK293) cells. In contrast, the exchange of non-conserved residues in the LBD that convert antagonist selectivity of GluK1–3 (GluK1-T503A, GluK2-A487T, GluK3-T489A, GluK1-N705S/S706N, GluK2-S689N/N690S, GluK3-N691S) did not alter the biosynthesis and trafficking of subunit proteins. Co-assembly of mutant GluK2 with an impaired LBD and wild type GluK5 subunits enables the cell surface expression of both subunits. However, [Ca2+]i imaging indicates that the occupancy of both GluK2 and GluK5 LBDs is required for the full activation of GluK2/GluK5 heteromeric KAR channels.

show abstract

Section: Introductionmentioning

confidence: 99%

Assembly and Trafficking of Homomeric and Heteromeric Kainate Receptors with Impaired Ligand Binding Sites

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…Their early pharmacological studies (Watkins 2000; Collingridge and Abraham 2021; Evans and Watkins 2021) provided compelling evidence that the major excitatory neurotransmitter L-glutamate activates three distinct subtypes of ligand-gated ion channels, still named after their agonists that preferentially activate them: α-amino-3-hydroxy-5methyl-4-isoxazolepropionic acid (AMPA), kainate and N-methyl-D-aspartate (NMDA) (Watkins and Jane 2006;Lodge 2009;Watkins 2000;Hansen et al 2021). Here we provide an update on kainate receptors (KARs).KARs are key players in the modulation of neuronal-network activity throughout the central nervous system (Contractor et al 2011;Lerma and Marques 2013;Molnár 2018). While other ionotropic glutamate receptors (AMPA and NMDA receptors) mainly operate postsynaptically, KARs are located at both presynaptic and postsynaptic sites where they modulate the release of the neurotransmitters glutamate and γ-aminobutyric acid (GABA), or mediate excitatory neurotransmission, respectively (Lerma and Marques 2013).…”

mentioning

confidence: 99%

“…KARs are key players in the modulation of neuronal-network activity throughout the central nervous system (Contractor et al 2011;Lerma and Marques 2013;Molnár 2018). While other ionotropic glutamate receptors (AMPA and NMDA receptors) mainly operate postsynaptically, KARs are located at both presynaptic and postsynaptic sites where they modulate the release of the neurotransmitters glutamate and γ-aminobutyric acid (GABA), or mediate excitatory neurotransmission, respectively (Lerma and Marques 2013).…”

mentioning

confidence: 99%