The NR2 subunits

The distribution of NR3A mRNA in the adult rat brain (X-ray film autoradiographs, coronal sections), am, amygdala cm, centromedial thalamic nucleus hy, hypothalamus Co, superior colliculus mg, medial geniculate nucleus pn, pontine nucleus pv, paraventricular thalamic nucleus rt, reticular thalamus. Scale bar, 1 mm (Ciabarra et al., 1995). 

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In contrast to AMPA receptors, NMDA receptor channels display a prominent Ca2+ permeability, which is largely independent ofthe subunit composition. It has been shown by mutational analysis that the Ca2+ permeability of recombinant NMDA receptors is dependent on a residue at a position equivalent to the Q/R site of AMPA subunits. Both NR1 and NR2 subunits contain an asparagine (N) residue at this position. Replacing this N with an R within the NR1 subunit led to the formation of NMDA receptors with a strongly reduced Ca2+ permeability, whereas exchanging N for Q in the NR2 subunit had only a small effect,... 

NMDA receptor agonists are typically short-chain dicarboxylic amino acids such as glutamate, aspartate and NMDA. Acting at a site on the NR2 subunit, glutamate is the most potent endogenous agonist in the... 

The NR2 subunit of the NMDA receptor binds to PDZ domains of PSD95 with its cytoplasmic C-terminus. PSD95 also binds a-actinin, which again binds to filamentous actin (F-actin), a main cytoskeletal protein in dendritic spines. In this manner PSD95 anchors the NMDA receptor to the cytoskeleton of the dendritic spine. 

In addition, it can be assumed that there are further cooperative effects between NR1 and NR2 subunits as the affinity of ligands for the glycines binding site of the NMDA receptor is dependent on the structure of the NR2 subunit (Honer et al., 1998). 

NR2 is the glutamate binding subunit. This subunit also contains the polyaminebinding site. It is generated as the product of four distinct genes (Yamakura and Shimoji, 1999). The NR2 subunit is responsible for most of the structural... 

NMDA receptors are clustered at postsynaptic sites where cytoplasmic adapter proteins anchor them to the cytoskeleton. Some adapter proteins contain a PDZ domain while others lack this. The PDZ domain is a protein-protein interaction motif of approximately 90 amino acids, which in most cases, binds their target proteins at the C-terminus ends. For example a PDZ domain protein, PSD-95, interacts with the C-terminus of the NR2 subunit. Its interaction with tubulin-based cytoskele-tal protein is mediated by a novel postsynaptic protein called CRIPT (Niethammer et al., 1998). Thus NR1 and NR2 subunits and their related proteins are crucial for efficient gating of NMDA receptor channels. 

Krupp,J.J., Vissel, B., Heinemann, S. F., and Westbrook, G. L. (1998). N-terminal domains in the NR2 subunit control desensitization of NMDA receptors. Neuron 20, 317-327. 

Neurons have a large excess of the NR1 subunit relative to the NR2 subunits this pool of NR1 is unassembled with NR2, exists primarily as a monomer, does not reach the cell surface, and is rapidly degraded if it does not assemble (19,20). 

NMDA receptors contain the essential NRl subunit in addition to the NR2 subunits that bind to PSD-95 family proteins. The cytoplasmic tail of NRl undergoes considerable alternative splicing (Hollmann et al., 1993). Although it does not bind to PSD-95, the C-terminal cytoplasmic tail of NRl does interact with several other cytoplasmic proteins (Fig. 2). Like NR2-PSD-95 interactions, these NRl-mediated interactions may play a role in synaptic targeting of NMDA receptors and NMDA receptor-associated signaling proteins. 

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