Dual Regulation of NMDA Receptor Functions by Direct Protein-Protein Interactions with the Dopamine D1 Receptor

Lee, Frank J.S.; Xue, Song; Lin, Pei; Vukusic, Brian; Chéry, Nadège; Wang, Yushan; Wang, Yu Tian; Niznik, Hyman B.; Yu, Xian‐Min; Liu, Fang

doi:10.1016/s0092-8674(02)00962-5

Cited by 485 publications

(470 citation statements)

References 45 publications

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“…D1-like receptors have a short third intracellular loop (IL3) and a long intracellular carboxyl terminus (Cterminus). In most cases, D1 receptors interact with the DRIPs through C-terminus rather than IL3 [22][23][24][25] . It has been reported that the substituted mutation of a hydrophobic motif, or the truncated mutation of C-terminus would disturb the cell surface targeting of D1R [22,23] .…”

Section: Discussionmentioning

confidence: 99%

“…D1R interacts with NMDA receptor subunits NR1 and NR2A and inhibits the NMDA-mediated current through its C-terminal tails [24] ; While D5R interacts with GABAa receptor 2 (short) subunit and enables mutually functional inhibition through it's C-terminus [25] . In a systematic binding study of the C-termini of all dopamine receptor subtypes, D5R but not D1R C-terminus selectively and strongly bound to a membrane-associated protein sorting nexin 1 (SNX1) [26] .…”

Section: Discussionmentioning

confidence: 99%

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神经细胞中多巴胺d1和d5受体不同亚细胞分布和胞内转运的特性

Jin

2009

Neurosci. Bull.

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Objective To explore the possible differential trafficking properties of the dopamine D1-like receptor subtypes, D1 receptor and D5 receptor. Methods To visualize distributions of dopamine D1-like receptor subtypes at subcellular level, the yellow and cyan variants of green fluorescent protein (GFP) were used to tag D1 and D5 receptors. After transfection with the tagged dopamine receptors, the neuroblastoma cells NG108-15 were treated with D1 agonist SKF38393 or acetylcholine (ACh). Then we observed the subcellular distributions of the tagged receptors under the confocal microscopy and tried to determine trafficking properties by comparing their distribution patterns before and after the drug treatment. Results In resting conditions, D1 receptors located in the plasma membrane of NG108-15 cells, while D5 receptors located in both plasma membrane and cytosol. With the pre-treatment of SKF38393, the subcellular distribution of D1 receptors was changed. The yellow particle-like fluorescence of tagged D1 receptors appeared in the cytosol, indicating that D1 receptors were internalized into cytosol from the cell surface. Same situation also occurred in ACh pre-treatment. In contrast, the subcellular distribution of D5 receptors was not changed after SKF38393 or ACh treatment, indicating that D5R was not translocated to cell surface. Interestingly, when D1 and D5 receptors were co-expressed in the same cell, both kept their distinct subcellular distribution patterns and the trafficking properties. Conclusion Our present study reveals that in NG108-15 nerve cells, dopamine D1 and D5 receptors exhibit differential subcellular distribution patterns, and only D1 receptor has a marked trafficking response to the drug stimulation. We further discuss the potential role of the differential trafficking properties of D1-like receptors in complex modulation of DA signaling.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

神经细胞中多巴胺d1和d5受体不同亚细胞分布和胞内转运的特性

Jin

2009

Neurosci. Bull.

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“…Besides short peptide sequences involved in G protein and arrestin binding, the remaining portions of these intracellular domains are presumably free to interact with other proteins. Using approaches such as co-immunoprecipitation and the yeast two-hybrid system, an increasing number of DRIPs are being identified [41][42][43]53,[68][69][70][71][72][73][74][75][76][77][78][79][80][81][82][83]. The confirmed DRIPs and their suggested functions are summarized in Table 1.…”

Section: Da Receptor-interacting Proteins (Drips)mentioning

confidence: 99%

“…D1, but not D5 receptors, can interact with NMDAR subunit 1 (NR1) and subunit 2A (NR2A), but not subunit 2B (NR2B) through the C terminal tails of these receptors [73]. These direct protein-protein interactions allow D1 receptors to inhibit, rather than potentiate, NMDAR-mediated currents in cultured neurons.…”

Section: D1 Drips In Dendritic Spinesmentioning

confidence: 99%

Dopaminergic signaling in dendritic spines

Yao

Spealman

Zhang

2008

Biochemical Pharmacology

108

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Dopamine regulates movement, motivation, reward, and learning and is implicated in numerous neuropsychiatric and neurological disorders. The action of dopamine is mediated by a family of seven-transmembrane G protein-coupled receptors encoded by at least five dopamine receptor genes (D1, D2, D3, D4, and D5), some of which are major molecular targets for diverse neuropsychiatric medications. Dopamine receptors are present throughout the soma and dendrites of the neuron, but accumulating ultrastructural and biochemical evidence indicates that they are concentrated in dendritic spines, where most of the glutamatergic synapses are established. By modulating local channels, receptors, and signaling modules in spines, this unique population of postsynaptic receptors is strategically positioned to control the excitability and synaptic properties of spines and mediate both the tonic and phasic aspects of dopaminergic signaling with remarkable precision and versatility. The molecular mechanisms that underlie the trafficking, targeting, anchorage, and signaling of dopamine receptors in spines are, however, largely unknown. The present commentary focuses on this important subpopulation of postsynaptic dopamine receptors with emphases on recent molecular, biochemical, pharmacological, ultrastructural, and physiological studies that provide new insights about their regulatory mechanisms and unique roles in dopamine signaling. The Central Dopaminergic Systems: An OverviewDopamine (DA) is a prototypical slow neurotransmitter that plays pivotal roles in a variety of cognitive, motivational, neuroendocrine, and motor functions [1][2]. Two major groups of DAcontaining neurons in the mammalian brain reside in the substantia nigra pars compacta (SN) and the ventral tegmental area (VTA) [3]. SN neurons form the nigrostriatal pathway, which projects mainly to the dorsal part of striatum where they control postural reflexes and initiation of movements. VTA neurons give rise to two pathways: the mesolimbic pathway, which projects to the subcortical and limbic nuclei, and the mesocortical pathway, which projects mainly to the cingulate, entorhinal and medial prefrontal cortices. Dysfunction of dopaminergic transmission in these major pathways has been implicated in an array of neurological and neuropsychiatric disorders, including Parkinson's disease, Huntington's diseases, schizophrenia, attention-deficit hyperactivity disorder (ADHD), and drug addiction [1][2]. Drugs targeting dopaminergic mechanisms are widely used to manage these and other conditions.The action of DA is mediated by a family of seven-transmembrane G protein-coupled receptors (GPCRs) encoded by at least five DA receptor genes (D1, D2, D3, D4, and D5) in the mammalian brain [4]. These receptors are classified into two subfamilies, the D1-class and Corresponding author: Wei-Dong Yao, Ph.D., Department of Psychiatry, Harvard Medical School, Beth Israel Deaconess Medical Center, New England Primate Research Center, One Pine Hill Drive, P.O. Box 9102, Southborough,...

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“…This is because SCH23390 can also affect the potency of drugs at the NMDA receptor, especially since it is known that D1 and NMDA receptors interact. [14][15][16] Although the blockade of D1 (by SCH23390) unmasks the functional D2 High states, 11 the addition of SCH23390 is only needed when using [ 3 H]raclopride to measure D2 receptors. [ 3 H]Domperidone, however, is a selective ligand for D2 that readily detects D2 High receptors without the addition of SCH23390.…”

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confidence: 99%

Dopamine receptor contribution to the action of PCP, LSD and ketamine psychotomimetics

2005

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Although phencyclidine and ketamine are used to model a hypoglutamate theory of schizophrenia, their selectivity for NMDA receptors has been questioned. To determine the affinities of phencyclidine, ketamine, dizocilpine and LSD for the functional high-affinity state of the dopamine D2 receptor, D2 High , their dissociation constants (K i ) were obtained on [ 3 H]domperidone binding to human cloned dopamine D2 receptors. Phencyclidine had a high affinity for D2 High with a K i of 2.7 nM, in contrast to its low affinity for the NMDA receptor, with a K i of 313 nM, as labeled by [ 3 H]dizocilpine on rat striatal tissue. Ketamine also had a high affinity for D2 High with a K i of 55 nM, an affinity higher than its 3100 nM K i for the NMDA sites. Dizocilpine had a K i of 0.3 nM at D2 High , but a K d of 1.8 nM at the NMDA receptor. LSD had a K i of 2 nM at D2 High . Because the psychotomimetics had higher potency at D2 High than at the NMDA site, the psychotomimetic action of these drugs must have a major contribution from D2 agonism. Because these drugs have a combined action on both dopamine receptors and NMDA receptors, these drugs, when given in vivo, test a combined hyperdopamine and hypoglutamate theory of psychosis. Keywords: dopamine receptor; phencyclidine; domperidone; ketamine; NMDA receptors; psychotomimetics While the clinical anti-dopaminergic actions of antipsychotic drugs are compatible with the hyperdopamine hypothesis of psychosis and schizophrenia, 1,2 the psychoses caused by glutamate antagonists such as phencyclidine or ketamine suggest a hypo-glutamate component in psychosis. [3][4][5] However, phencyclidine also lowers plasma prolactin 6 and elicits rotation, 7 suggesting a direct or indirect dopaminemimetic action of phencyclidine.Although phencyclidine and ketamine are not selective for glutamate NMDA receptors, 8 the precise affinities of these drugs for dopamine D2 receptors need to be clarified in order to determine their dopaminergic and non-dopaminergic components of action. More specifically, although phencyclidine had a dissociation constant of 37 000 nM at the D2 receptor in rat striatal homogenate, 8 phencyclidine had a dissociation constant of 1.3 nM for the functional high-affinity site of the cloned D2 receptor, or the D2 High receptor. 9 This apparent discrepancy may be resolved by the recent finding that dopamine itself has a dissociation constant of 3000 nM when competing vs [ 3 H]raclopride at striatal D2 receptors, but has a dissociation constant of 1.5 nM at the D2 High receptor when the link between dopamine D1 and D2 receptors is blocked by the D1 antagonist SCH23390. 10 The link between D1 and D2 receptors arises from several sources, including the colocalization of dopamine D1 and D2 receptors in at least 50% of the medium spiny neurons in the striatum, the cooperation and mutual potentiation of D1 and D2 agonists on various behaviors, and the biochemical conversion of D2 receptors from their functional high-affinity state, D2 High , into their low-affinity state, D2 Lo...

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Dual Regulation of NMDA Receptor Functions by Direct Protein-Protein Interactions with the Dopamine D1 Receptor

Cited by 485 publications

References 45 publications

神经细胞中多巴胺d1和d5受体不同亚细胞分布和胞内转运的特性

神经细胞中多巴胺d1和d5受体不同亚细胞分布和胞内转运的特性

Dopaminergic signaling in dendritic spines

Dopamine receptor contribution to the action of PCP, LSD and ketamine psychotomimetics

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