GluN2

GluN2 is a family of NMDA receptor subunits encoded by GRIN2A-D, that together with GluN1 form NMDA-type glutamate receptors with heterotetrameric architecture. The four GluN2 subunits (A-D) confer distinct kinetic, pharmacological, and signaling properties.

Each receptor typically comprises two GluN1 and two GluN2 subunits; the GluN2 C-terminal domains interact with intracellular scaffolding proteins (PSD-95, others) to organize signaling complexes and trafficking. Subunit composition affects agonist affinity, channel kinetics, Mg2+ block relief, Ca2+ permeability, and sensitivity to modulators such as zinc and ifenprodil.

Expression patterns vary developmentally and regionally. GluN2B is abundant in early development and in several forebrain regions; GluN2A increases with maturation; GluN2C and GluN2D have more restricted expression, notably in cerebellum, thalamus, and some interneuron populations. The combination of two GluN2 subunits with two GluN1 units forms functional receptors with diverse properties.

They mediate voltage-dependent Ca2+ influx in response to glutamate, contributing to synaptic plasticity mechanisms like LTP and LTD. Subunit composition shapes synaptic signaling, plasticity thresholds, and susceptibility to excitotoxic injury.

Alterations in GRIN2 genes or GluN2-containing receptors are linked to neurodevelopmental and psychiatric conditions, epilepsy, and neurodegenerative disorders. They are also targets of pharmacological research for mood disorders, pain, and ischemic injury.