GluR5 and GluR6 Kainate Receptor Subunits Coexist in Hippocampal Neurons and Coassemble to Form Functional Receptors

Paternain, Ana V.; Herrera, María Teresa Alarcón; Nieto, M. Ángela; Lerma, Juan

doi:10.1523/jneurosci.20-01-00196.2000

Cited by 180 publications

(164 citation statements)

References 42 publications

(39 reference statements)

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“…The GluR5 and KA2 plasmids were cotransfected in 1:1 or 1:3 ratios, whereas a ratio of 1:2.5 was used for GluR6 and GluR5 and 1:10 when GluR6 was cotransfected with KA2. These ratios were sufficient for GluR6 to generate a large proportion of heteromeric receptors with GluR5 and KA2 subunits (Paternain et al, 2000(Paternain et al, , 2003. Indeed, this fact was systematically evaluated by applying AMPA and (RS)-2-␣-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA), which activates heteromeric GluR6 -GluR5 or GluR6 -KA2 but not homomeric GluR6.…”

Section: Methodsmentioning

confidence: 99%

“…Highly fluorescent cells were identified and selected for recording. In our hands, GluR5 (up to 10 g) did not yield any current when transfected alone (Paternain et al, 2000(Paternain et al, , 2003. Therefore, we used HEK293 cells stably expressing human GluR5-1a(Q) to evaluate homomeric GluR5 receptors as described previously (Varming et al, 2001).…”

Section: Methodsmentioning

confidence: 99%

“…Although GluR5-GluR7 can form functional homomeric receptor channels, KA1 and KA2 must form heteromers with these GluR subunits to form receptors with distinct properties (Herb et al, 1992). Although CA1 interneurons mostly express GluR5 and GluR6 subunits (Bureau et al, 1999;Paternain et al, 2000), KA2 may also be present in these cells (Wisden and Seeburg, 1993;Bureau et al, 1999). The activation of these KARs in hippocampal interneurons produces two distinct effects on pyramidal cells: an increase in spontaneous IPSCs, indicative of the depolarization of the somatodendritic compartments in interneurons; and a reduction in the amplitude of evoked IPSC, probably produced by a depression of GABA release.…”

Section: Introductionmentioning

confidence: 99%

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A Mosaic of Functional Kainate Receptors in Hippocampal Interneurons

Christensen¹,

Paternain²,

Selak³

et al. 2004

J. Neurosci.

118

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Although some physiological functions of kainate receptors (KARs) still remain unclear, recent advances have highlighted a role in synaptic physiology. In hippocampal slices, kainate depresses GABA-mediated synaptic inhibition and increases the firing rate of interneurons. However, the sensitivity to agonists of these responses differs, suggesting that the presynaptic and somatic KARs have a distinct molecular composition. Hippocampal interneurons express several distinct KAR subunits that can assemble into heteromeric receptors with a variety of pharmacological properties and that, in principle, could fulfill different roles. To address which receptor types mediate each of the effects of kainate in interneurons, we used new compounds and mice deficient for specific KAR subunits. In a recombinant assay, 5-carboxyl-2,4-di-benzamido-benzoic acid (NS3763) acted exclusively on homomeric glutamate receptor subunit 5 (GluR5), whereas 3S,4aR,6S,8aR-6-((4-carboxyphenyl)methyl) 1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid (LY382884) antagonized homomeric GluR5 and any heteromeric combination containing GluR5 subunits. In hippocampal slices, LY382884, but not NS3763, was able to prevent kainate-induced depression of evoked IPSC. In contrast, neither prevented the concomitant increase in spontaneous IPSC frequency. The selectivity of these compounds was seen additionally in knock-out mice, such that they were inactive in GluR5 Ϫ/Ϫ mice but completely effective in GluR6 Ϫ/Ϫ mice. Our data indicate that in wild-type mice, CA1 interneurons express heteromeric GluR6 -KA2 receptors in their somatic compartments and GluR5-GluR6 or GluR5-KA2 at presynaptic terminals. However, functional compensation appears to take place in the null mutants, a new pharmacological profile emerging more compatible with the activity of homomeric receptors in both compartments: GluR5 in GluR6 Ϫ/Ϫ mice and GluR6 in GluR5 Ϫ/Ϫ mice.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Mosaic of Functional Kainate Receptors in Hippocampal Interneurons

Christensen¹,

Paternain²,

Selak³

et al. 2004

J. Neurosci.

118

View full text Add to dashboard Cite

show abstract

“…In hippocampal interneurons, KARs are likely heteromers composed of both GluR5 and GluR6 subunits Paternain et al, 2000). In these heteromeric KARs, association with GluR6a would facilitate trafficking to the plasma membrane.…”

Section: Functional Significance: Splice Variants In Native Receptorsmentioning

confidence: 99%

“…KA1 and KA2 associate with these subunits to form heteromeric receptors with distinct pharmacological properties (Bettler and Mulle, 1995;Lerma et al, 2001). GluR5 and GluR6 also coassemble to generate recombinant and native receptors with novel functional properties (Cui and Mayer, 1999;Mulle et al, 2000;Paternain et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Subunit Composition and Alternative Splicing Regulate Membrane Delivery of Kainate Receptors

Jaskolski¹,

Coussen²,

Nagarajan³

et al. 2004

J. Neurosci.

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Kainate receptors (KARs) are heteromeric ionotropic glutamate receptors (GluRs) that play various roles in the regulation of synaptic transmission. The KAR subunits GluR5 and GluR6 exist under different splice variant isoforms in the C-terminal domain (GluR5a, GluR5b, GluR5c, GluR6a, GluR6b). The differential role of KAR subunit splice variants is presently unknown. In transfected COS-7 cells and neurons from wild-type and GluR5 ϫ GluR6 mice, we have found that the subcellular localization and membrane delivery differed between these splice variants. GluR6a was highly expressed at the plasma membrane. GluR6b, GluR5a, and GluR5b were detected at lower levels in the plasma membrane and mainly colocalized with calreticulin in the endoplasmic reticulum (ER). GluR5c was strongly retained in the ER by an RXR motif. GluR6a acted as a key subunit splice variant promoting surface expression of ER-retained subunit splice variants when assembled in heteromeric KARs. Surface expression of GluR6a was independent of its PDZ (postsynaptic density-95/discs large/zona occludens-1) binding motif and was promoted by a stretch of four basic amino acid residues at its C terminus. Overall, splice variants and subunit composition of KARs regulate receptor trafficking from the endoplasmic reticulum to the plasma membrane.

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Ionotropic glutamate receptors: Which ones, when, and where in the mammalian neocortex

Hadžić

Jack

Wahle

2016

J of Comparative Neurology

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A multitude of 18 iGluR receptor subunits, many of which are diversified by splicing and RNA editing, localize to >20 excitatory and inhibitory neocortical neuron types defined by physiology, morphology, and transcriptome in addition to various types of glial, endothelial, and blood cells. Here we have compiled the published expression of iGluR subunits in the areas and cell types of developing and adult cortex of rat, mouse, carnivore, bovine, monkey, and human as determined with antibody- and mRNA-based techniques. iGluRs are differentially expressed in the cortical areas and in the species, and all have a unique developmental pattern. Differences are quantitative rather than a mere absence/presence of expression. iGluR are too ubiquitously expressed and of limited use as markers for areas or layers. A focus has been the iGluR profile of cortical interneuron types. For instance, GluK1 and GluN3A are enriched in, but not specific for, interneurons; moreover, the interneurons expressing these subunits belong to different types. Adressing the types is still a major hurdle because type-specific markers are lacking, and the frequently used neuropeptide/CaBP signatures are subject to regulation by age and activity and vary as well between species and areas. RNA-seq reveals almost all subunits in the two morphofunctionally characterized interneuron types of adult cortical layer I, suggesting a fairly broad expression at the RNA level. It remains to be determined whether all proteins are synthesized, to which pre- or postsynaptic subdomains in a given neuron type they localize, and whether all are involved in synaptic transmission. J. Comp. Neurol. 525:976-1033, 2017. © 2016 Wiley Periodicals, Inc.

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GluR5 and GluR6 Kainate Receptor Subunits Coexist in Hippocampal Neurons and Coassemble to Form Functional Receptors

Cited by 180 publications

References 42 publications

A Mosaic of Functional Kainate Receptors in Hippocampal Interneurons

A Mosaic of Functional Kainate Receptors in Hippocampal Interneurons

Subunit Composition and Alternative Splicing Regulate Membrane Delivery of Kainate Receptors

Ionotropic glutamate receptors: Which ones, when, and where in the mammalian neocortex

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