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Glutamate MDAreceptor subunit epsilon-2, also known as ''N''-methyl D-aspartate receptor subtype 2B (NMDAR2B or NR2B), is a
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''GRIN2B''
gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.


NMDA receptors

''N''-methyl-D-aspartate (
NMDA ''N''-methyl--aspartic acid, or ''N''-methyl--aspartate (NMDA), is an amino acid derivative that acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor. Unl ...
) receptors are a class of ionotropic glutamate receptors. The NMDA receptor channel has been shown to be involved in
long-term potentiation In neuroscience, long-term potentiation (LTP) is a persistent strengthening of synapses based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neuron ...
, an activity-dependent increase in the efficiency of synaptic transmission thought to underlie certain kinds of memory and learning. NMDA receptor channels are heterotetramers composed of two molecules of the key receptor subunit NMDAR1 (
GRIN1 Glutamate MDAreceptor subunit zeta-1 is a protein that in humans is encoded by the ''GRIN1'' gene. The protein encoded by this gene is a critical subunit of N-methyl-D-aspartate receptors, members of the glutamate receptor channel superfamily w ...
) and two drawn from one or more of the four NMDAR2 subunits: NMDAR2A (
GRIN2A Glutamate MDAreceptor subunit epsilon-1 is a protein that in humans is encoded by the ''GRIN2A'' gene. With 1464 amino acids, the canonical GluN2A subunit isoform is large. GluN2A-short isoforms specific to primates can be produced by alternative ...
), NMDAR2B (GRIN2B), NMDAR2C ( GRIN2C), and NMDAR2D ( GRIN2D). The NR2 subunit acts as the agonist binding site for
glutamate Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a Essential amino acid, non-essential nutrient for humans, meaning that ...
, one of the predominant excitatory neurotransmitter receptors in the mammalian brain.


Function

NR2B has been associated with age- and
visual The visual system is the physiological basis of visual perception (the ability to detect and process light). The system detects, transduces and interprets information concerning light within the visible range to construct an image and buil ...
-experience-dependent plasticity in the
neocortex The neocortex, also called the neopallium, isocortex, or the six-layered cortex, is a set of layers of the mammalian cerebral cortex involved in higher-order brain functions such as sensory perception, cognition, generation of motor commands, ...
of
rat Rats are various medium-sized, long-tailed rodents. Species of rats are found throughout the order Rodentia, but stereotypical rats are found in the genus ''Rattus''. Other rat genera include '' Neotoma'' (pack rats), '' Bandicota'' (bandicoo ...
s, where an increased NR2B/NR2A ratio correlates directly with the stronger excitatory LTP in young animals. This is thought to contribute to experience-dependent refinement of developing cortical circuits. Engineered to overexpress GRIN2B in their brains, mice and rats exhibit improved mental function. The "Doogie" mouse performed twice as well on one learning test.


Ligands

* Besonprodil * CERC-301, a selective NR2B receptor antagonist * Eliprodil *
Ethanol Ethanol (also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound with the chemical formula . It is an Alcohol (chemistry), alcohol, with its formula also written as , or EtOH, where Et is the ps ...
- apparent induction of dephosphorylation of the NR2B Tyr1472 residue by STEP, leading to reduced receptor function * Ifenprodil * Rislenemdaz * EVT-101, a selective NR2B receptor antagonist. This compound was tested as a potentially fast-acting antidepressant. In 2011 it was voluntarily withdrawn from a Phase II clinical study in treatment-resistant depression due to an unsatisfactory toxicity profile. * Felbamate, an anticonvulsant that is also a
positive allosteric modulator In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a receptor to change that receptor's response to stimuli. Some of them, like benzodiazepines or alcohol, function as psychoactive drugs. The site that ...
for the GABAA receptor * Ro-25-6981 (also known as MI-4), a selective NR2B receptor antagonist * Traxoprodil, a selective NR2B receptor antagonist *
Toluene Toluene (), also known as toluol (), is a substituted aromatic hydrocarbon with the chemical formula , often abbreviated as , where Ph stands for the phenyl group. It is a colorless, water Water is an inorganic compound with the c ...
- noncompetitive antagonist


Interactions

GRIN2B has been shown to interact with: * Actinin, alpha 2, * DLG2, *
DLG3 Disks large homolog 3 (DLG3) also known as neuroendocrine-DLG or synapse-associated protein 102 (SAP-102) is a protein that in humans is encoded by the ''DLG3'' gene. DLG3 is a member of the membrane-associated guanylate kinase (MAGUK) superfami ...
, *
DLG4 PSD-95 (postsynaptic density protein 95) also known as SAP-90 (synapse-associated protein 90) is a protein that in humans is encoded by the ''DLG4'' (discs large homolog 4) gene. PSD-95 is a member of the membrane-associated guanylate kinase (MA ...
, *
EXOC4 Exocyst complex component 4 is a protein that in humans is encoded by the ''EXOC4'' gene. Function The protein encoded by this gene is a component of the exocyst complex, a multiple protein complex essential for targeting exocytic vesicles to ...
, * LIN7B, and *
RICS The Royal Institution of Chartered Surveyors (RICS) is a global professional body for those working in the Built Environment, Construction, Land, Property and Real Estate. The RICS was founded in London in 1868. It works at a cross-governmental ...
.


See also

*
NMDA receptor The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and predominantly Ca2+ ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other ...
*
Glutamate receptor Glutamate receptors are synaptic and non synaptic receptors located primarily on the membranes of neuronal and glial cells. Glutamate (the conjugate base of glutamic acid) is abundant in the human body, but particularly in the nervous system ...


References


Further reading

* * * * * * * * * * * * * * * * * * * {{Ligand-gated ion channels Ionotropic glutamate receptors