Sequence determinants on the NR2A and NR2B subunits of NMDA receptor responsible for specificity of phosphorylation by CaMKII

Mayadevi, Madhavan; Praseeda, Mullasseril; Kumar, K. Sudheer; Omkumar, Ramakrishnapillai V.

doi:10.1016/s0167-4838(02)00315-1

Cited by 48 publications

(40 citation statements)

References 19 publications

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“…1). In murine NR2B, CaMKII␣ binds at one site (1292-1308Mayadevi et al, 2002) that is conserved in fish NR2B (Harvey-Girard and Dunn, 2003). These data suggest that NR2B-CaMKII␣ interactions are conserved in fish, whereas NR2A-CaMKII interactions are partially lost.…”

Section: Conserved Nmdar Downstream Effectorsmentioning

confidence: 85%

“…Calcium/calmodulin-dependent kinase II␣ (CaMKII␣) binds directly to mammalian NMDARs via amino acids motifs in the carboxyl-terminal domain of NR2A or NR2B (Gardoni et al, 1999(Gardoni et al, , 2001aMayadevi et al, 2002;Omkumar et al, 1996) and is involved in long-term synaptic plasticity induced by NMDAR activity (Lisman et al, 2002;Lisman and Zhabotinsky, 2001;Xia and Storm, 2005). CaMKII␣ binds to the mammalian NR2A subunit (Gardoni et al, 1999(Gardoni et al, , 2001b at two possible sites (murNR2A: 1412-1419 and 1278 -1298; Gardoni et al, 2001a;Mayadevi et al, 2002). The first site (1412-1419) is completely absent in aptNR2A, although the second one (aptNR2A: 1278 -1298) remains partially conserved with the phosphorylation site motif still in place (Fig.…”

Section: Conserved Nmdar Downstream Effectorsmentioning

confidence: 99%

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Regulated expression of N‐methyl‐D‐aspartate receptors and associated proteins in teleost electrosensory system and telencephalon

Harvey‐Girard

Dunn

Maler

2007

J of Comparative Neurology

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Several types of N-methyl-D-aspartate (NMDA) receptor-dependent synaptic plasticity are characterized by differences in polarity, induction parameters, and duration, which depend on the interactions of NMDARs with intracellular synaptic and signaling proteins. Here, we examine the NMDAR signaling components in the brain of the weakly electric fish Apteronotus leptorhynchus. Compared with mammalian orthologs, high levels of sequence conservation for known functional sites in both NMDAR subunits (NR1, NR2A-C) and signaling proteins (fyn tyrosine kinase, RasGRF-1 and -2) were found. In situ hybridization analysis demonstrated that, similar to the case in the adult mammal brain, NR2A and NR2B are expressed at moderate levels in most brain regions and at very high levels in the dorsal telencephalon. RasGRF-1 and fyn have a similar distribution and appear to be coexpressed with NR2B in telencephalic regions known to support learning and long-term memory. Both NR2A and NR2B are highly expressed in pyramidal cells of the electrosensory lateral line lobe (ELL) known to exhibit the short-term synaptic plasticity that underlies adaptive feedback cancellation of redundant sensory input. In contrast, nonplastic pyramidal cells expressed only the NR2A subunit. Furthermore, field recordings show that ifenprodil-sensitive NR2B-containing NMDARs predominate for the plastic feedback input to ELL pyramidal cells. However, RasGRF-1 and fyn are expressed only at low levels in a subset of these pyramidal cells. Our data suggest that NMDAR functions are highly conserved between fish and mammals and that synaptic plasticity dynamics in different brain regions are related to the expression patterns of the synaptic signaling proteins interacting with NMDARs.

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Section: Conserved Nmdar Downstream Effectorsmentioning

confidence: 85%

Section: Conserved Nmdar Downstream Effectorsmentioning

confidence: 99%

Regulated expression of N‐methyl‐D‐aspartate receptors and associated proteins in teleost electrosensory system and telencephalon

Harvey‐Girard

Dunn

Maler

2007

J of Comparative Neurology

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“…This finding is consistent with previous experiments that have shown that NR2B is a critical substrate of CaMKII during synaptic plasticity and learning. Their association with each other occurs during Ca 2ϩ increases in the cell (Omkumar et al, 1996), and catalytic site-mediated binding of CaMKII displays specificity for the phosphorylation site of NR2B (Strack et al, 2000;Mayadevi et al, 2002). Autophosphorylation at Thr 286 of CaMKII is associated with high-affinity binding of the enzyme to NR2B, whereas there is little or no binding of CaMKII to NR1 or NR2A subunits by this mechanism (Strack and Colbran, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…During a transient elevation of intracellular Ca 2ϩ through the NMDA receptor, CaMKII translocates to the synapses of pyramidal neurons (Shen and Meyer, 1999;Shen et al, 2000) where it can interact with and modulate a number of proteins at the postsynaptic density (PSD) that are critical for synaptic plasticity, including AMPA (Barria et al, 1997;Derkach et al, 1999) and NMDA receptors (Buchs and Muller, 1996;Strack and Colbran, 1998;Leonard et al, 1999;Strack et al, 2000). The association of CaMKII with the NR2B subunit of the NMDA receptor appears to be particularly important; previous work has demonstrated that an interaction between CaMKII and NR2B may be critical for synaptic plasticity (Omkumar et al, 1996;Strack and Colbran, 1998;Bayer et al, 2001;Mayadevi et al, 2002). During activation by CaM binding, CaMKII undergoes autophosphorylation at a critical threonine residue (Thr 286 ) that transforms it to persistently active, calcium-independent state Hudmon and Schulman, 2002).…”

Section: Introductionmentioning

confidence: 99%

Pavlovian Fear Conditioning Regulates Thr²⁸⁶Autophosphorylation of Ca²+/Calmodulin-Dependent Protein Kinase II at Lateral Amygdala Synapses

Rodrigues¹,

Farb²,

Bauer³

et al. 2004

J. Neurosci.

124

111

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Ca2ϩ /calmodulin-dependent protein kinase II (CaMKII) plays a critical role in synaptic plasticity and memory formation in a variety of learning systems and species. The present experiments examined the role of CaMKII in the circuitry underlying pavlovian fear conditioning. First, we reveal by immunocytochemical and tract-tracing methods that ␣CaMKII is postsynaptic to auditory thalamic inputs and colocalized with the NR2B subunit of the NMDA receptor. Furthermore, we show that fear conditioning results in an increase of the autophosphorylated (active) form of ␣CaMKII in lateral amygdala (LA) spines. Next, we demonstrate that intra-amygdala infusion of a CaMK inhibitor, 1-[NO-bis-1,5-isoquinolinesulfonyl]-N-methyl-L-tyrosyl-4-phenylpiperazine, KN-62, dose-dependently impairs the acquisition, but not the expression, of auditory and contextual fear conditioning. Finally, in electrophysiological experiments, we demonstrate that an NMDA receptor-dependent form of long-term potentiation at thalamic input synapses to the LA is impaired by bath application of KN-62 in vitro. Together, the results of these experiments provide the first comprehensive view of the role of CaMKII in the amygdala during fear conditioning.

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“…Recently, some studies have focused on the importance of NMDA receptor subunit composition and signaling at the postsynaptic cell. Biochemical studies have shown highaffinity binding between the catalytic domain of CaMKII and the C-tail of NR2B subunit of the NMDA receptor (Strack and Colbran, 1998;Leonard et al, 1999;Strack et al, 2000;Bayer et al, 2001;Mayadevi et al, 2002). Many brain regions, including the hippocampus, show changes from Temporal lobe glutamate receptors in severe mental illness M Beneyto et al containing predominantly NR2B to containing NR2A in response to different stimuli (Monyer et al, 1994;Sheng et al, 1994).…”

Section: Altered Ionotropic Glutamate Receptor Expression In the Medimentioning

confidence: 99%

Abnormal Glutamate Receptor Expression in the Medial Temporal Lobe in Schizophrenia and Mood Disorders

Beneyto

Kristiansen

Oni-Orisan

et al. 2007

Neuropsychopharmacol

378

216

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Pharmacological and anatomical evidence suggests that abnormal glutamate neurotransmission may be associated with the pathophysiology of schizophrenia and mood disorders. Medial temporal lobe structural alterations have been implicated in schizophrenia and to a lesser extent in mood disorders. To comprehensively examine the ionotropic glutamate receptors in these illnesses, we used in situ hybridization to determine transcript expression of N-methyl-D-aspartate (NMDA), a-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), and kainate receptor subunits in the medial temporal lobe of subjects with schizophrenia, bipolar disorder (BD), or major depression (MDD). We used receptor autoradiography to assess changes in glutamate receptor binding in the same subjects. Our results indicate that there are region-and disorder-specific abnormalities in the expression of ionotropic glutamate receptor subunits in schizophrenia and mood disorders. We did not find any changes in transcript expression in the hippocampus. In the entorhinal cortex, most changes in glutamate receptor expression were associated with BD, with decreased GluR2, GluR3, and GluR6 mRNA expression. In the perirhinal cortex we detected decreased expression of GluR5 in all three diagnoses, of GluR1, GluR3, NR2B in both BD and MDD, and decreased NR1 and NR2A in BD and MDD, respectively. Receptor binding showed NMDA receptor subsites particularly affected in the hippocampus, where MK801 binding was reduced in schizophrenia and BD, and MDL105,519 and CGP39653 binding were increased in BD and MDD, respectively. In the hippocampus AMPA and kainate binding were not changed. We found no changes in the entorhinal and perirhinal cortices. These data suggest that glutamate receptor expression is altered in the medial temporal lobe in schizophrenia and the mood disorders. We propose that disturbances in glutamate-mediated synaptic transmission in the medial temporal lobe are important factors in the pathophysiology of these severe psychiatric illnesses.

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Sequence determinants on the NR2A and NR2B subunits of NMDA receptor responsible for specificity of phosphorylation by CaMKII

Cited by 48 publications

References 19 publications

Regulated expression of N‐methyl‐D‐aspartate receptors and associated proteins in teleost electrosensory system and telencephalon

Regulated expression of N‐methyl‐D‐aspartate receptors and associated proteins in teleost electrosensory system and telencephalon

Pavlovian Fear Conditioning Regulates Thr²⁸⁶Autophosphorylation of Ca²+/Calmodulin-Dependent Protein Kinase II at Lateral Amygdala Synapses

Abnormal Glutamate Receptor Expression in the Medial Temporal Lobe in Schizophrenia and Mood Disorders

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Sequence determinants on the NR2A and NR2B subunits of NMDA receptor responsible for specificity of phosphorylation by CaMKII

Cited by 48 publications

References 19 publications

Regulated expression of N‐methyl‐D‐aspartate receptors and associated proteins in teleost electrosensory system and telencephalon

Regulated expression of N‐methyl‐D‐aspartate receptors and associated proteins in teleost electrosensory system and telencephalon

Pavlovian Fear Conditioning Regulates Thr286Autophosphorylation of Ca2+/Calmodulin-Dependent Protein Kinase II at Lateral Amygdala Synapses

Abnormal Glutamate Receptor Expression in the Medial Temporal Lobe in Schizophrenia and Mood Disorders

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Pavlovian Fear Conditioning Regulates Thr²⁸⁶Autophosphorylation of Ca²+/Calmodulin-Dependent Protein Kinase II at Lateral Amygdala Synapses