Assembly and cell surface presentation of NMDA receptors

NMDA tetramers assemble in the endoplasmic reticulum and traffic to the plasma membrane as part of transport vesicles. NMDA receptor subunits undergo N-glycosylation, which impacts their trafficking from the endoplasmic reticulum to the plasma membrane. Trafficking efficiency may vary among different subunits of NMDARs. Mechanistic details, such as glycosyl transferases involved and the type of sugar side chains added, are not known.

As there are eight splicing isoforms of GluN1, four different GluN2 and two different GluN3 proteins, many different combinations of NMDAR subunits are possible, but only a handful of distinct NMDAR receptors have been experimentally confirmed and functionally studied. The composition of NMDARs affects trafficking, spatial (including synaptic) localization, ligand preference, channel conductivity and downstream signal transmission. Prevalent NMDARs differ at different stages of neuronal development, in different regions of the central nervous system, and at different levels of neuronal activity. For review, please refer to Lau and Zukin 2007, Traynelis et al. 2010, Paoletti et al. 2013, Pérez-Otaño et al. 2016, Iacobucci and Popescu 2017.