Selective RNA editing and subunit assembly of native glutamate receptors

Puchalski, Ralph B.; Louis, Jean Claude; Brose, Nils; Traynelis, Stephen F.; Egebjerg, Jan; Kukekov, Valery G.; Wenthold, Robert J.; Rogers, Scott W.; Lin, Fan; Moran, Thomas M.; Morrison, John H.; Heinemann, Stephen F.

doi:10.1016/0896-6273(94)90464-2

Cited by 155 publications

(103 citation statements)

References 56 publications

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“…4). Thus, the oligodendrocyte progenitor cell line CG4 as well as cultured purified cortical O-2A progenitor cells express all known AMPA and kainate receptor subunits, with the exception of the GluR1 and GluR5 subunits (10,18). These findings are consistent with the observations reported here in differentiated oligodendrocytes derived from the perinatal optic nerve.…”

Section: Discussionsupporting

confidence: 83%

“…Glutamate Receptor Immunocytochemistry. Cells at 3 to 7 days in culture were washed with sodium PBS, fixed in 4% paraformaldehyde in PBS for 20 min, and then processed for immunocytochemistry as described by Puchalski et al (10). Primary antibodies were applied for 45 min, at concentrations of 2.5 g͞ml for GluR1, GluR2͞3, and GluR4 (all from Chemicon), 1 g͞ml for GluR5͞6͞7 (PharMingen), 6 g͞ml for KA2 (generously provided by R. J. Wenthold, National Institutes of Health, Bethesda, MD), 2 g͞ml for NMDAR1 (Chemicon), and 4 g͞ml for NMDAR2A͞B (Chemicon).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Glutamate receptor-mediated toxicity in optic nerve oligodendrocytes

Matute

Sánchez‐Gómez

Martínez‐Millán

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

328

267

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In cultured oligodendrocytes isolated from perinatal rat optic nerves, we have analyzed the expression of ionotropic glutamate receptor subunits as well as the effect of the activation of these receptors on oligodendrocyte viability. Reverse transcription-PCR, in combination with immunocytochemistry, demonstrated that most oligodendrocytes differentiated in vitro express the ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits GluR3 and GluR4 and the kainate receptor subunits GluR6, GluR7, KA1 and KA2. Acute and chronic exposure to kainate caused extensive oligodendrocyte death in culture. This effect was partially prevented by the AMPA receptor antagonist GYKI 52466 and was completely abolished by the non-N-methyl-Daspartate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), suggesting that both AMPA and kainate receptors mediate the observed kainate toxicity. Furthermore, chronic application of kainate to optic nerves in vivo resulted in massive oligodendrocyte death which, as in vitro, could be prevented by coinfusion of the toxin with CNQX. These findings suggest that excessive activation of the ionotropic glutamate receptors expressed by oligodendrocytes may act as a negative regulator of the size of this cell population.The main function of oligodendrocytes is to myelinate axons in the vertebrate central nervous system. This cell type develops mostly soon after the majority of neurons are generated and have extended their axons and, therefore, it is likely that neurons play an important role in regulating oligodendrocyte development. In the rat optic nerve, the first fully differentiated oligodendrocytes appear after birth, and the definitive mature population of oligodendrocytes is reached around 6 weeks later (1, 2). The proliferation and the survival of oligodendrocytes depend, respectively, on the electrical activity of neighboring axons and in the reciprocal contacts they establish (for a recent review, see ref.3). Axon to oligodendrocyte signaling results in the generation of the precise number of oligodendrocytes necessary to myelinate entirely a given population of axons. Unfortunately, little information is available about the molecules participating in this signaling process.Oligodendrocytes express neurotransmitter receptors including those activated by glutamate (4). This excitatory amino acid acts at various types of receptors, which can be grouped into two major categories: ionotropic receptors, which gate membrane ion channels permeable to cations; and metabotropic receptors, which are coupled to G proteins. Ionotropic receptors are classified into ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate, and N-methyl-Daspartate (NMDA) subtypes, according to their preferred agonist. Molecular cloning has revealed that each receptor subtype is composed of several subunits with high homology within each receptor class (reviewed in ref. 5). Thus, AMPA receptors are formed by GluR1-4, kainate receptors by GluR5-7 and KA1-2, and NMDA rece...

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Section: Discussionsupporting

confidence: 83%

Section: Methodsmentioning

confidence: 99%

Glutamate receptor-mediated toxicity in optic nerve oligodendrocytes

Matute

Sánchez‐Gómez

Martínez‐Millán

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

328

267

View full text Add to dashboard Cite

show abstract

“…Immunoprecipitation experiments from detergent extract of neurons show a similar segregation of subunits between subfamilies (14 -16, 55). Whether a small amount of receptor complexes containing both AMPA and kainate receptor subunits is present in neurons is still a matter of debate (15,55). The number of mixed complexes in neurons might be reduced not only by preferential subunit assembly, but also by differential targeting and stabilization of receptor complexes.…”

Section: Discussionmentioning

confidence: 99%

Subtype-specific Assembly of α-Amino-3-hydroxy-5-methyl-4-isoxazole Propionic Acid Receptor Subunits Is Mediated by Their N-terminal Domains

Leuschner

Hoch

1999

Journal of Biological Chemistry

110

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Glutamate receptors (GluR) are oligomeric protein complexes formed by the assembly of four or perhaps five subunits. The rules that govern the selectivity of this process are not well understood. Here, we expressed combinations of subunits from two related GluR subfamilies in COS7 cells, the ␣-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainate receptors. By co-immunoprecipitation experiments, we assessed the ability of AMPA receptor subunits to assemble into multimeric complexes. Subunits GluR1-4 associated with indistinguishable efficiency with each other, whereas the kainate receptor subunits GluR6 and 7 showed a much lower degree of association with GluR1. Using chimeric receptors and truncation fragments of subunits, we show that this assembly specificity is determined by N-terminal regions of these subunits and that the most N-terminal domain of GluR2 together with a membrane anchor efficiently associates with GluR1.

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“…This is exemplified by the different representations between the flip and flop transcripts of fGluRlct and fGluR2c~ as obtained by quantitative RT-PCR and colony hybridization methods (Tables 1 and 2). Direct analysis of the RT-PCR product by primer extension in the presence of a chain-terminator has been performed to analyze the extent of RNA editing of rat non-NMDA receptors [17]. The sequence difference between the flip and flop transcripts is more prominent than that between the edited and unedited transcripts; consequently, a one-step amplification with an exon-specific primer is sufficiently specific to amplify a particular splicing variant.…”

Section: Discussionmentioning

confidence: 99%