Differential expression and co-assembly of NMDAξ1 and &amp;epsiv; subunits in the mouse cerebellum during postnatal development

Didier, Michel; Xu, Min; Berman, Steve A.; Bursztajn, Sherry

doi:10.1097/00001756-199511000-00036

Cited by 22 publications

(17 citation statements)

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“…4). This finding is in line with previous studies, in which NR2C mRNA was observed in the cerebellum around birth (Monyer et al, 1994;Watanabe et al, 1994), whereas the NR2C protein was not detected before P9 by western blot analysis (Didier et al, 1995). Likewise, NMDA receptors with functional characteristics of the NR1 /2C subunit combination (Stern et al, 1992) were not detectable before P13 (Farrant et al, 1994).…”

Section: Expression Of Nr Mrna and Proteinsupporting

confidence: 92%

“…4 and Table 1). These results are in line with western blotting experiments and data obtained from cerebellar granule cells in culture (Didier et al, 1995;Vallano et al, 1996;Wang et al, 1995). Thus, the immature cerebellum seems to be characterized by only one NMDA receptor subtype (NR 1/2B), whereas with ongoing maturation at least two new receptor subtypes-NRJ/NR2C and NR1/ NR2A-appear to be expressed (Table 1).…”

Section: Rearrangement Of Nr Expression During Postnatal Developmentsupporting

confidence: 86%

“…Thus, the immature cerebellum seems to be characterized by only one NMDA receptor subtype (NR 1/2B), whereas with ongoing maturation at least two new receptor subtypes-NRJ/NR2C and NR1/ NR2A-appear to be expressed (Table 1). The combination NR1 /NR2A/NR2C is unlikely to exist, as immunoprecipitation experiments in mouse cerebellum detected receptors with the subunit combinations NR1 I 2C and NRJ /2A but not the triple subunit combination NR1/2A/2C (Didier et al, 1995). In line with these data, only one main channel conductance, resembling that of NR1 /2A or NR1 /2B recombinant receptors, was recorded in granule cells from early postnatal brain, but two different main channel conductances, resembling those of recombinant NR1/2C and NR1/ 2A or NR1/2B receptors (Stern et al, 1992), were recorded from cerebellar granule cells of the adult rat brain (Farrant et al, 1994).…”

Section: Rearrangement Of Nr Expression During Postnatal Developmentmentioning

confidence: 99%

“…However, knowledge on the time course and regional variations of the expression of NR proteins during development is derived from western blotting and immunoprecipitation experiments Didier et al, 1995;Wang et al, 1995;Luo et al, 1996;Portera-Cailliau et al, 1996). Studies with a higher spatial resolution are only available for NR1 Johnson et al, 1996;Rema and Ebner, 1996) and the NR2D subunit (Wenzel et al, 1996).…”

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confidence: 99%

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NMDA Receptor Heterogeneity During Postnatal Development of the Rat Brain: Differential Expression of the NR2A, NR2B, and NR2C Subunit Proteins

Wenzel

Fritschy

Möhler

et al. 1997

Journal of Neurochemistry

408

254

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Abstract:Changes in the expression of the NMDA receptor subunits (NRs) NR2A, 2B, and 2C were investigated in histo blots of the developing rat brain with subunitspecific antisera. At birth, the NR2B subunit was detected almost ubiquitously, the NR2A subunit staining was faint and restricted to the hippocampus, cerebral cortex, and striatum, and no NR2C subunit immunoreactivity was detected. During the first 3 postnatal weeks, the NR2B subunit became confined to forebrain structures, whereas the NR2A immunoreactivity became abundantly expressed throughout the brain. The NR2C immunoreactivity emerged 5 days after birth in the olfactory bulb, thalamus, and vestibular nuclei and became very intense after 10 days in cerebellar granule cells, its primary site of expression in adulthood. After 3 weeks, NR2A and NR2B immunoreactivity decreased to adult levels, whereas NR2C immunoreactivity remained unchanged. The patterns of distribution of the subunit proteins were in agreement with those of their corresponding mRNAs, as monitored by in situ hybridization histochemistry, although the mRNA translation appeared to be delayed by several days in certain areas. Our results reveal a progressive increase in the heterogeneity of NMDA receptors due to the comparably late onset of NR2A and NR2C subunit expression and by the area-specific rearrangement of NR2B subunit expression following birth. Key Words: NMDA receptor -Subunit -specific antisera -DevelopjiientHisto blots-Rat. J. Neurochem. 68, 469-478 (1997).N-Methyl-D-aspartate (NMDA) receptors are glutamate-activated cation channels, characterized by a high Ca 2~INa~permeability ratio, a voltage-dependent Mg 2+ block, a requirement for glycine as coagonist, and slow activation and deactivation kinetics (Nowak et al

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Section: Expression Of Nr Mrna and Proteinsupporting

confidence: 92%

Section: Rearrangement Of Nr Expression During Postnatal Developmentsupporting

confidence: 86%

Section: Rearrangement Of Nr Expression During Postnatal Developmentmentioning

confidence: 99%

mentioning

confidence: 99%

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NMDA Receptor Heterogeneity During Postnatal Development of the Rat Brain: Differential Expression of the NR2A, NR2B, and NR2C Subunit Proteins

Wenzel

Fritschy

Möhler

et al. 1997

Journal of Neurochemistry

408

254

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“…However, there is evidence that triheteromeric receptors, which contain more than one type of NR2 subunit, exist within many brain regions, including the cortex (Sheng et al, 1994;Didier et al, 1995;Chazot and Stephenson, 1997;Luo et al, 1997), cerebellum (Chazot et al, 1994;Cathala et al, 2000;Brickley et al, 2003), and substantia nigra (Jones and Gibb, 2005). Coexpression of the NR1, NR2A, and NR2D subunits in Xenopus oocytes yields a receptor with many characteristics intermediate between NR1/2A and NR1/2D receptors (Cheffings and Colquhoun, 2000).…”

Section: Discussionmentioning

confidence: 99%

NMDA Receptor NR2 Subunit Dependence of the Slow Component of Magnesium Unblock

Clarke¹,

Johnson²

2006

J. Neurosci.

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Weaver cerebellar granule neurons show altered expression of NMDA receptor subunits bothin vivo andin vitro

et al. 1999

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Biochemical, immunocytochemical, and molecular biological techniques were used to investigate the expression of N‐methyl‐D‐aspartate (NMDA) receptor subunits in migration‐deficient weaver mouse cerebellum in vivo and in primary cultures of the vermal weaver granule neurons with or without a rescue by verapamil. We found that both NMDAR1(ζ1) message and protein were expressed by the weaver granule neurons in situ. Immunocytochemical and biochemical analyses indicated that granule neurons of the weaver cerebellum expressed R1(ζ1) and R2A(ϵ1) subunits but showed little expression of the R2B(ϵ2) subunit. In weaver cerebellum, the R2B(ϵ2) subunit was primarily expressed in nerve fibers of the internal granule cell layer and white matter. Reverse‐transcriptase–polymerase chain reaction followed by sequence analysis of the R1(ζ1) subunit indicated that the ζ1 subunit amplicons of both normal and weaver cerebella were identical, and that splice variants with exon 22 (1‐2) and with or without exon 5 (a/b) or exon 21 (1‐4) were detectable. The R2A(ϵ1), and R2B(ϵ2) subunits of the normal and weaver mouse cerebellum revealed no primary structural differences between the normal and weaver NMDA receptor subunits or the cloned mouse NMDA receptor subunits. In vermal cultures, normal granule neurons expressed all three NMDA receptor subunits (ζ1, ϵ1, and ϵ2), whereas the weaver neurons failed to express the ϵ2 subunit. Rescue of the weaver neurons by verapamil induced expression of the ϵ2 protein along the granule neuronal surfaces. The present results suggest that lack of the ϵ2 subunit in the weaver cerebellum may relate to the lack of functional NMDA receptors and/or to the migratory failure of the weaver granule neurons. Our data further suggest that NMDA receptor–mediated neurotoxicity is an unlikely mediator of neuronal death of the weaver granule neurons. In fact, down‐regulation of the NMDA receptor expression and function may be a protective measure of the weaver granule neurons to reduce calcium entry via these receptors. © 1999 John Wiley & Sons, Inc. J Neurobiol 38: 441–454, 1999

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Differential expression and co-assembly of NMDAξ1 and ϵ subunits in the mouse cerebellum during postnatal development

Cited by 22 publications

References 0 publications

NMDA Receptor Heterogeneity During Postnatal Development of the Rat Brain: Differential Expression of the NR2A, NR2B, and NR2C Subunit Proteins

NMDA Receptor Heterogeneity During Postnatal Development of the Rat Brain: Differential Expression of the NR2A, NR2B, and NR2C Subunit Proteins

NMDA Receptor NR2 Subunit Dependence of the Slow Component of Magnesium Unblock

Weaver cerebellar granule neurons show altered expression of NMDA receptor subunits bothin vivo andin vitro

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