ABSTRACT

The majority of glutamatergic synapses are located on dendritic spines and possess a submembraneous protein network known as postsynaptic density (PSD). A prominent feature of the core proteins of the PSD is their insolubility in detergents like Triton X100 (Kennedy, 1997). Functional NMDA receptors are integral membrane proteins and, as such, are contained in the postsynaptic membrane. However, NMDA receptors are also insoluble in Triton X-100 and NR2 subunits appear as core components in preparations of the PSD (Moon et al., 1994; Allison et al., 1998). Thus, NMDA receptors are tightly anchored in the PSD. NMDA receptor subunits exhibit very long cytoplasmic C-terminal tails compared to other glutamate receptor subtypes, and the anchoring of NMDA receptors in the PSD is likely to be the result of an interaction between the C-terminal tails of the NMDA receptor subunits and PSD proteins. Indeed, a surprisingly large variety of intracellular proteins have been identified that interact with the cytoplasmic portion of NMDA receptors (Table 3.1).