Regional and developmental heterogeneity in splicing of the rat brain NMDAR1 mRNA

Laurie, David J.; Seeburg, Peter H.

doi:10.1523/jneurosci.14-05-03180.1994

Cited by 382 publications

(246 citation statements)

References 23 publications

(65 reference statements)

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“…Relatively higher uses of the C2Ј cassette in the cerebellum and of the C1 and C2 cassettes in the cerebral cortex are generally consistent with previous studies by in situ hybridization and immunoblot analyses (Laurie and Seeburg, 1994;Al-Hallaq et al, 2001). In the present study, C-terminal cassette-dependent differences of the GluR1 subunit were also appreciated in the brain in vivo.…”

Section: Terminus-dependent Self-er Export Mechanisms In Neurons Insupporting

confidence: 92%

NMDA Receptor GluRϵ/NR2 Subunits Are Essential for Postsynaptic Localization and Protein Stability of GluRζ1/NR1 Subunit

Abe¹,

Fukaya²,

Yagi³

et al. 2004

J. Neurosci.

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In NMDA receptors, GluR⑀/NR2 subunits strictly require the GluR1/NR1 subunit to exit from endoplasmic reticulum (ER) to the cell surface in vitro and to the postsynapse in vivo, whereas C terminus-dependent self-surface delivery has been demonstrated for the GluR1 subunit in vitro. To test whether this leads to C terminus-dependent self-postsynaptic expression in neurons in vivo, we investigated the GluR1 subunit in cerebellar granule cells lacking two major GluR⑀ subunits, GluR⑀1/NR2A and GluR⑀3/NR2C. In the mutant cerebellum, synaptic labeling for the GluR1 subunit containing the C2 (GluR1-C2) or C2Ј (GluR1-C2Ј) cassette was reduced at mossy fiber-granule cell synapses to the extrasynaptic level. The loss was not accompanied by decreased transcription and translation levels, increased extrasynaptic labeling, or ER accumulation. Quantitative immunoblot revealed substantial reductions in the mutant cerebellum of GluR1-C2 and GluR1-C2Ј. The most severe deficit was observed in the postsynaptic density (PSD) fraction: mutant levels relative to the wild-type level were 12.3 Ϯ 3.3% for GluR1-C2 and 17.0 Ϯ 4.6% for GluR1-C2Ј. The GluR1 subunit carrying the C1 cassette (GluR1-C1) was, although low in cerebellar content, also reduced to 12.7 Ϯ 3.5% in the mutant PSD fraction. Considering a trace amount of other GluR⑀ subunits in the mutant cerebellum, the severe reductions thus represent that the GluR1 subunit, by itself, is virtually unable to accumulate at postsynaptic sites, regardless of C-terminal forms. By protein turnover analysis, the degradation of the GluR1 subunit was accelerated in the mutant cerebellum, being particularly rapid for that carrying the C2 cassette. Therefore, accompanying expression of GluR⑀ subunits is essential for postsynaptic localization and protein stability of the GluR1 subunit.

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Section: Terminus-dependent Self-er Export Mechanisms In Neurons Insupporting

confidence: 92%

NMDA Receptor GluRϵ/NR2 Subunits Are Essential for Postsynaptic Localization and Protein Stability of GluRζ1/NR1 Subunit

Abe¹,

Fukaya²,

Yagi³

et al. 2004

J. Neurosci.

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“…A previous single cell PCR study has shown that NMDAR1 mRNA is present within dendrites (Miyashiro et al, 1994), which is consistent with results showing clear dendritic localization of NMDAR1 mRNA within dendrites of cultured hippocampal neurons (Benson 1997;present study). However, previous localization studies in vivo have not shown any evidence of a dendritic distribution (Moriyoshi et al, 1991;Laurie and Seeburg, 1994). This discrepancy most likely reflects very low basal levels of dendritic NMDAR1 mRNA, which become suprathreshold for overt detectability after perforant path lesion.…”

Section: Localization Of Nmdar1 Mrna Within Dendritesmentioning

confidence: 77%

Differential Subcellular Regulation of NMDAR1 Protein and mRNA in Dendrites of Dentate Gyrus Granule Cells after Perforant Path Transection

Gazzaley¹,

Benson²,

Huntley³

et al. 1997

J. Neurosci.

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Unilateral transection of the excitatory perforant path results in the acute deafferentation of a segregated zone on the distal dendrites of hippocampal dentate gyrus granule cells (i.e., outer molecular layer), followed by sprouting, reactive synaptogenesis, and a return of physiological and behavioral function. To investigate cellular mechanisms underlying NMDA receptor plasticity in response to such extensive synaptic reorganization, we quantitatively evaluated changes in intensity levels of NMDAR1 immunofluorescence and NMDAR1 mRNA hybridization within subcellular compartments of dentate gyrus granule cells 2, 5, and 9 d after perforant path lesions. There were no significant changes in either measure at 2 d postlesion. However, at 5 and 9 d postlesion, during the period of axonal sprouting and synaptogenesis, there was an increase in NMDAR1 immunolabeling that was restricted to the dendritic segments of the denervated outer molecular layer and the granule cell somata. In contrast, NMDAR1 mRNA levels at 5 and 9 d postlesion increased throughout the full extent of the molecular layer, including both denervated and nondenervated segments of granule cell dendrites. These findings reveal that NMDAR1 mRNA is one of a limited population of mRNAs that is transported into dendrites and further suggest that in response to terminal proliferation and sprouting, increased mRNA transport occurs throughout the full dendritic extent, whereas increased local protein synthesis is restricted to denervated regions of the dendrites whose afferent activity is perturbed. These results begin to elucidate the dynamic postsynaptic subcellular regulation of receptor subunits associated with synaptic plasticity after denervation.

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“…In rat brain, ζ1-a splice forms have been found to be the most abundant form of splice variants and are expressed all throughout the brain (Laurie and Seeburg, 1994;Laurie et al, 1995). A higher expression of ζ1-a mRNA in the 26-month old animals indicated that there was a higher amount of receptor protein without the N1 insert.…”

Section: Mrna Expression Of ζ1 Splice Formsmentioning

confidence: 99%

“…Depending on whether the N1, C1 or C2 cassettes are present or absent, they make eight different splice variants. The splice variants of NR1 (ζ1) present in the receptor complex determine a number of properties of the ion channel, such as affinity to agonist and antagonists, zinc modulation and spatio-temporal expression in the brain (Dingledine et al, 1999;Laurie and Seeburg, 1994;Prybylowski and Wolfe, 2000;Zhong et al, 1995). Due to these properties, differential effects of aging on the different splice variants could lead to important changes in the physiology and pharmacology of the NMDA receptor in the aged brain.…”

Section: Introductionmentioning

confidence: 99%

Relationship between mRNA expression of splice forms of the ζ1 subunit of the N-methyl-d-aspartate receptor and spatial memory in aged mice

Das

Magnusson

2008

Brain Research

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Age-related changes in the protein and mRNA expression of some of the splice forms of the ζ1 (NR1) subunit of the NMDA receptor have been seen in mice and rats. The present study was designed to determine whether individual splice forms of the ζ1 subunit of the NMDA receptor within prefrontal/frontal cortical regions contribute to memory deficits during aging and whether experience in learning tasks can influence the expression of the splice forms. mRNA expression of 4 splice forms (ζ1-1, ζ1-3, ζ1-a and ζ1-b) and mRNA for all known splice forms (ζ1-pan) were examined by in situ hybridization. mRNA for C-terminal splice forms, ζ1-1 (+C1 and +C2 cassettes) and ζ1-3 (+C1 and +C2′), showed significant declines during aging in several brain regions even though overall ζ1-pan mRNA expression was not significantly affected by aging. This suggests that these splice forms are more influenced by aging than the subunit as a whole. There was an increase in the expression of ζ1-a (−N1 cassette) splice form in the behaviorally-experienced old mice relative to the younger groups. Old mice with high levels of mRNA expression for the ζ1-a splice form in orbital cortex showed the best performances in the working memory task, but the poorest performances in the cued, associative learning task. These results suggest that there is a complex interaction between ζ1 splice form expression and performance of memory tasks during aging.

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Regional and developmental heterogeneity in splicing of the rat brain NMDAR1 mRNA

Cited by 382 publications

References 23 publications

NMDA Receptor GluRϵ/NR2 Subunits Are Essential for Postsynaptic Localization and Protein Stability of GluRζ1/NR1 Subunit

NMDA Receptor GluRϵ/NR2 Subunits Are Essential for Postsynaptic Localization and Protein Stability of GluRζ1/NR1 Subunit

Differential Subcellular Regulation of NMDAR1 Protein and mRNA in Dendrites of Dentate Gyrus Granule Cells after Perforant Path Transection

Relationship between mRNA expression of splice forms of the ζ1 subunit of the N-methyl-d-aspartate receptor and spatial memory in aged mice

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