Assembly with the NR1 Subunit Is Required for Surface Expression of NR3A-Containing NMDA Receptors

Pérez‐Otaño, Isabel; Schulteis, Christine T.; Contractor, Anis; Lipton, Stuart A.; Trimmer, James S.; Sucher, Nikolaus J.; Heinemann, Stephen F.

doi:10.1523/jneurosci.21-04-01228.2001

Cited by 241 publications

(236 citation statements)

References 43 publications

Supporting

Mentioning

213

Contrasting

Unclassified

Order By: Relevance

“…On the contrary, receptors containing NR2C or NR2D subunits give rise to 'lowconductance' channels with a lower sensitivity to Mg 2+ ions and permeability principally to Na + ions. The NR3 subunits are thought to be regulatory in nature, since they do not form functional channels with NR1 subunits but co-assemble with NR1/NR2 complexes forming 'low-conductance' channels [168].…”

Section: Structure and Function Of Nmda Receptorsmentioning

confidence: 99%

Role of Altered Structure and Function of NMDA Receptors in Development of Alcohol Dependence

Nagy

Kolok²,

Boros³

et al. 2005

View full text Add to dashboard Cite

Long-term alcohol exposure gives rise to development of physical dependence on alcohol in consequence of changes in certain neurotransmitter functions. Accumulating evidence suggests that the glutamatergic neurotransmitter system, especially the N-methyl-D-aspartate (NMDA) type of glutamate receptors is a particularly important site of ethanol's action, since ethanol is a potent inhibitor of the NMDA receptors (NMDARs) and prolonged ethanol exposition leads to a compensatory "upregulation" of NMDAR mediated functions supposedly contributing to the occurrence of ethanol tolerance, dependence as well as the acute and delayed signs of ethanol withdrawal.Recently, expression of different types of NMDAR subunits was found altered after long-term ethanol exposure. Especially, the expression of the NR2B and certain splice variant forms of the NR1 subunits were increased in primary neuronal cultures treated intermittently with ethanol. Since NMDA ion channels with such an altered subunit composition have increased permeability for calcium ions, increased agonist sensitivity, and relatively slow closing kinetics, the abovementioned alterations may underlie the enhanced NMDAR activation observed after long-term ethanol exposure. In accordance with these changes, the inhibitory potential of NR2B subunit-selective NMDAR antagonists is also increased, demonstrating excellent potency against alcohol withdrawal-induced in vitro cytotoxicity. Although in vivo data are few with these compounds, according to the effectiveness of the classic NMDAR antagonists in attenuation, not only the physical symptoms,but also some affective and motivational components of alcohol withdrawal, novel NR2B subunit selective NMDAR antagonists may offer a preferable alternative in the pharmacotherapy of alcohol dependence.

show abstract

Section: Structure and Function Of Nmda Receptorsmentioning

confidence: 99%

Role of Altered Structure and Function of NMDA Receptors in Development of Alcohol Dependence

Nagy

Kolok²,

Boros³

et al. 2005

View full text Add to dashboard Cite

show abstract

“…NMDA receptors (NMDARs) consist of the obligatory NR1 subunit in combination with NR2A-D and NR3A-B subunits (Sheng et al, 1994;Perez-Otano et al, 2001). NR2A and NR2B subunits have longer intracellular C-tails than the NR1 subunit, which endow them the capability to interact with neighboring postsynaptic density proteins (Osten et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Metaplastic Regulation of Long-Term Potentiation/Long-Term Depression Threshold by Activity-Dependent Changes of NR2A/NR2B Ratio

Chen²,

Gu³

et al. 2009

Journal of Neuroscience

View full text Add to dashboard Cite

In vivo experience induces changes in synaptic NMDA receptor (NMDAR) subunit components, which are correlated with subsequent modifications of synaptic plasticity. However, little is known about how these subunit changes regulate the induction threshold of subsequent plasticity. At hippocampal Schaffer collateral-CA1 synapses, we first examined whether a recent history of neuronal activity could affect subsequent synaptic plasticity through its actions on NMDAR subunit components. We found that prior activity history produced by priming stimulations (PSs) across a wide range of frequencies (1-100 Hz) could induce bidirectional changes in the NR2A/NR2B ratio, which governs the threshold for subsequent long-term potentiation/long-term depression (LTP/LTD). Manipulating the NR2A/NR2B ratio through partial NR2 subunit blockade mimicked the PS regulation of the LTP/LTD threshold. Our results demonstrate that activity-dependent changes in the NR2A/NR2B ratio can be critical factors in metaplastic regulation of the LTP/LTD threshold.

show abstract

“…In addition, NR3A can assemble with NR1 (ref. 10) to form functional glycine receptors 12 . Although intracellular carboxy-terminal domains of NR1 and NR2 subunits have been implicated in synaptic targeting, intracellular trafficking, downstream signal transduction and channel regulation 7 , the role of NR3 intracellular domains in NMDAR function remains unknown.…”

mentioning

confidence: 99%

Endocytosis and synaptic removal of NR3A-containing NMDA receptors by PACSIN1/syndapin1

et al. 2006

Self Cite

View full text Add to dashboard Cite

A key step in glutamatergic synapse maturation is the replacement of developmentally expressed N-methyl-D-aspartate receptors (NMDARs) with mature forms that differ in subunit composition, electrophysiological properties and propensity to elicit synaptic plasticity. However, the mechanisms underlying the removal and replacement of synaptic NMDARs are poorly understood. Here we demonstrate that NMDARs containing the developmentally regulated NR3A subunit undergo rapid endocytosis from the dendritic plasma membrane in cultured rat hippocampal neurons. This endocytic removal is regulated by PACSIN1/syndapin1, which directly and selectively binds the carboxy-terminal domain of NR3A through its NPF motifs and assembles a complex of proteins including dynamin and clathrin. Endocytosis of NR3A by PACSIN1 is activity dependent, and disruption of PACSIN1 function causes NR3A accumulation at synaptic sites. Our results reveal a new activity-dependent mechanism involved in the regulation of NMDAR expression at synapses during development, and identify a brain-specific endocytic adaptor that confers spatiotemporal and subunit specificity to NMDAR endocytosis.Stabilization and maturation of synapses is central to neural circuit formation. During development, excitatory synapses in the central nervous system are remodeled in response to

show abstract

Assembly with the NR1 Subunit Is Required for Surface Expression of NR3A-Containing NMDA Receptors

Cited by 241 publications

References 43 publications

Role of Altered Structure and Function of NMDA Receptors in Development of Alcohol Dependence

Role of Altered Structure and Function of NMDA Receptors in Development of Alcohol Dependence

Metaplastic Regulation of Long-Term Potentiation/Long-Term Depression Threshold by Activity-Dependent Changes of NR2A/NR2B Ratio

Endocytosis and synaptic removal of NR3A-containing NMDA receptors by PACSIN1/syndapin1

Contact Info

Product

Resources

About