NMDA receptor subunits

Receptor subunits are numbered al, j61, etc. where there are more than one subunit of that type. Between different a subunits in any family there is around 60-70% amino-acid sequence homology whereas between a and subtypes, for example, there is normally around only 40% sequence homology. Mouse NMDA receptor subunits are denoted by the Greek letters and g while rat and human are indicated as shown. 

V-methyl-D-aspartate (NMDA) receptors have multiple regulatory sites. To date, three NMDA receptor subunit families have been identified, one represented by a single gene (NR1, encoding a protein of -900 amino acids), the... 

Akbarian S, Sucher NJ, Bradley D, Tafazzoli A, Trinh D, Hetrick WP, Potkin SG, Sandman CA, Bunney WE Jr, Jones EG. (1996). Selective alterations in gene expression for NMDA receptor subunits in prefrontal cortex of schizophrenics. J Neurosci. 16(1) 19-30. 

Kornau HC, Schenker LT, Kennedy MB, Seeburg PH. 1995. Domain interaction between NMDA receptor subunits and... 

Charpak S, Gahwiler BH, Do KQ, Knopfel T (1990) Potassiiun conductances in hippocampal neurons blocked by excitatory aminoacid transmitters. Natme 347 765-767 Chatterton JE, Awobuluyi M, Premkiunar LS, et al (2002) Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits. Nature 415 793-798 Chen HX, Roper SN (2004) Tonic activity of metabotropic glutamate receptors is involved in developmental modification of short-term plasticity in the neocortex. J Neurophysiol 92 838-844... 

NT199 Delibas, N., R. Ozcankaya, 1. Altuntas, and R. Sutcu. Effect of cigarette smoke on lipid peroxidation, antioxidant enzymes and NMDA receptor subunits 2A and 2B concentration in rat hippocampus. Cell Biochem Funct 2003 21(1) 69-73. 

Furthermore, in rodents a member of a third class of NMDA receptor subunits (NR3A) has been cloned (Sucher et al., 1995). Expression of this NR3A subunit together with NR1 and NR2 subunits has been shown to cause in vitro an attenuation of the NMDA-induced ion fluxes and consequently NR3A knock-out mice show in vivo enhanced NMDA receptor activity (Das et al., 1998). Meanwhile a second member (NR3B) of this third class of subunit with comparable features has been cloned from mouse genome (Nishi et al., 2001). 

A., Rayudu, P. V., Cheung, W., Chen, H.-S., V., Lipton, S. A., Nakanishi, N. Increased NMDA current and spine density in mice lacking the NMDA receptor subunit NR3A, Nature 1998, 393, 377-381. 

Laube, B., Hirai, H., Sturgess, M., Betz, H., Kuhse, J. Molecular determinants of agonist discrimination by NMDA receptor subunits Analysis of the glutamate binding site on the NR2B subunit. Neuron 1997, 18, 493-503. 

Suzuki, T. and Okumura-Noji, K. NMDA receptor subunits e1 (NR2A) and e2 (NR2B) are substrates for Fyn in the postsynaptic density fraction isolated from the rat brain, Biochem. Biophys. Res. Comm. 1995, 216, 582-588. 

Structure and Distribution of NMDA Receptor Subunits in Brain... 

Another mechanism of synaptic dysfunction in AD may involve amyloid ft peptide (Aft a 40 to 42 amino acid peptide). A marked increase in Aft levels occurs in brain tissue from AD patients. A ft inhibits glutamatergic neurotransmission and reduces synaptic plasticity (Snyder et al., 2005). Treatment of cortical neuronal cultures with Aft facilitates endocytosis of NMDA receptor. Aft-mediated endo-cytosis of NMDA receptor requires the a-1 nicotinic receptor, protein phosphatase 2B, and the tyrosine phosphatase STEP. Dephosphorylation of the NMDA receptor subunit NR2B at Tyrl472 correlates with receptor endocytosis. The addition of a y-secretase inhibitor not only reduces Aft but also restores surface expression of NMDA receptors, suggesting that A plays an important role in the regulation of NMDA and AMPA receptor trafficking (Snyder et al., 2005 Morishita et al., 2005). 

Landwehrmeyer GB, Standaert DG, Testa CM, Penney JB, Jr., Young AB (1995) NMDA receptor subunit mRNA expression by projection neurons and interneurons in rat striatum. J Neurosci 15 5297-5307. 

Chatterton JE, Awobuluyi M, Premkumar LS, Takahashi H, Talantova M, et al. 2002. Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits. 

Di Maria E, Gulli R, Begni S, De Luca A, Bignotti S, et al. 2004. Variations in the NMDA receptor subunit 2B gene (GRIN2B) and schizophrenia A case-control study. Am J Med Genet B Neuropsychiatr Genet 128 27-29. 

Yashiro K, Philpot BD. 2008. Regulation of NMDA receptor subunit expression and its implications for LTD, LTP, and metaplasticity. Neuropharmacology 55 1081-1094. 

Okamato S-i, Sherman K, Bai G, Lipton SA. 2002. Effect of the ubiquitous transcription factors, SP1 and MAZ, on NMDA receptor subunit type 1 (NR1) expression during neuronal differentiation. Mol Brain Res 107 89-96. 

Ozaki M, Sasner M, Yano R, Lu HS, Buonanno A. 1997. Neuregulin-beta induces expression of an NMDA-receptor subunit. Nature 390 691-694. 

Meador-Woodruff and Healy, 2000). A study of the NMDA receptor subunits NR I, NR2A, and NR2B found an increase of NR2B mRNA and a decrease of NR1 mRNA in the hippocampus in schizophrenia.(Gao et al., 2000), but this has not been replicated in subsequent studies (see Kristiansen et al., this volume). 

Selective alterations in gene expression for NMDA receptor subunits in prefrontal cortex of schizophrenics. J Neurosci 16 19-30. 

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