Transmembrane AMPA receptor regulatory protein gamma-2 (TARP gamma-2)

Transmembrane AMPA receptor regulatory protein gamma-2 (TARP gamma-2), widely known as Stargazin, is a critical auxiliary subunit that controls the life cycle and signaling of AMPA-type glutamate receptors (AMPARs). It serves a dual function: it is essential for the trafficking of AMPARs from the endoplasmic reticulum to the postsynaptic membrane and for the subsequent stabilization of these receptors at the synapse (UniProt Q9Y698). Additionally, Stargazin profoundly alters the biophysical properties of the AMPAR channel, increasing its open-probability and slowing the rates of desensitization and deactivation (PubMed: 10917526). Because of its high expression in the cerebellum and cerebral cortex, it is a major factor in maintaining excitatory balance; its dysfunction is strongly linked to absence seizures and other forms of epilepsy (PubMed: 18431299). In drug development, TARP gamma-2 is a key target for achieving regional selectivity in the brain, as drugs like Decanoic acid have shown the ability to inhibit AMPARs in a TARP-dependent manner (PubMed: 27037871). Targeting the TARP-AMPAR complex offers a therapeutic window to treat neurological disorders while potentially mitigating the severe motor side effects associated with non-selective glutamate receptor blockade.

Other names

StargazinCACNG2Calcium channel voltage-dependent subunit gamma-2Voltage-dependent calcium channel gamma-2 subunitTARP-2

Modulation of AMPA receptor surface expression and channel gating kinetics through direct protein-protein interaction, specifically slowing desensitization and deactivation.