Trafficking and Targeting of NMDA Receptors

Metabotropic NMDA receptor function is required for β-amyloid–induced synaptic depression

“…In contrast to the hippocampal synapses of immature age in our model system, mature synapses generally contain low amounts of GluN2B/GluN1 and predominantly contain GluN2A/GluN1 and hetero-trimeric GluN2A/ GluN2B/GluN1 receptors (25). GluN2B/GluN1s are expressed in mature neurons but are predominantly located in extrasynaptic regions of the cell membrane (45). A recent study suggests that Aβ oligomers can effect a change through these extrasynaptic GluN2B/ GluN1s (16).…”

Tyrosine Phosphorylation of the NMDA Receptor Following Cerebral Ischaemia

“…Although the stoichiometry of subunits remains to be definitively resolved, endogenous NMDA receptors are thought to require the assembly of two GluN1 subunits with either two GluN2 subunits, or a combination of GluN2 and GluN3 subunits [19,236]. Regardless of their ultimate arrangement, similar to other iGluRs, NMDARs are thought to be held within the endoplasmic reticulum until they assemble in a manner sufficient to permit counteraction of a retention signal [183].…”

Two N-glycosylation Sites in the GluN1 Subunit Are Essential for Releasing N-methyl-d-aspartate (NMDA) Receptors from the Endoplasmic Reticulum

“…Recent studies suggest that abnormal regulation of NMDARs plays a fundamental role in the development of many neurological and psychiatric disorders, including Alzheimer disease, Parkinson disease, epilepsy, and schizophrenia (1,4). Therefore, understanding the mechanisms that regulate both the trafficking and function of NMDARs is essential for developing novel treatments for these disorders.…”

“…NMDARs contain a combination of seven principal subunits (GluN1, GluN2A through GluN2D, and GluN3A and GluN3B), all of which share a common membrane topology that includes four membrane domains (called M1 through M4), an extracellular N terminus, an extracellular loop connecting the M3 and M4 domains, and an intracellular C terminus (3). Both the number and type of NMDARs at the cell surface are regulated at multiple levels, including protein synthesis, subunit assembly, processing in the endoplasmic reticulum (ER), intracellular trafficking via the Golgi apparatus (GA), internalization, recycling, and degradation (1)(2)(3)(4).…”