Mechanisms For NMDA Receptor Subunits Assembly

N-methyl-D-aspartate (NMDA) receptors, one of three main classes of ionotropic glutamate receptor, play major roles in synaptic plasticity, synaptogenesis and excitotoxicity. Different from non-NMDA receptors, NMDA receptors are thought to be hetero-tetrameric complex mainly composed of NR1 and NR2 subunits. When expressed alone in heterogenous cells, such as HEK293 cells, the NR subunit cannot leave the ER and express in the cell membrane because of the ER retention signals in subunit. Correct assembly is the prerequisite for NMDA receptor trafficking to the cell surface, for the ER retention signals would be covered after the subunits assembling as a heterotetramer. However, the mechanisms underlying the NMDA receptor assembly remain poorly understood. To identify regions in subunits that mediate the receptor assembly, we made a series of truncated and chimeric DNA constructs. Combined with the biochemistry method and FRET measurement in living cells, we detected the assembly of these mutated NMDA receptor subunits.We found that the large N terminus are not required for the assembly of NMDA receptors, however, transmembrane region of subunit is required for the assembly of NMDA receptor subunits and could mediate the subunits assembly, both for the homomer and heteromer.