GluA1

GluA1 is an ionotropic glutamate receptor subunit that forms AMPA receptors, which mediate the majority of fast excitatory synaptic transmission in the mammalian central nervous system. The protein is encoded by the GRIA1 gene.

GluA1 belongs to the AMPA receptor family, together with GluA2, GluA3, and GluA4. AMPA receptors are tetrameric ion channels assembled from these subunits; GluA1 can form homomeric receptors or combine with GluA2 or GluA3 to create heteromeric receptors.

Expression and localization: GluA1 is widely expressed throughout the brain, with high levels in the hippocampus, cortex, and striatum, and is localized to excitatory synapses.

Regulation and trafficking: Synaptic strength is controlled by activity-dependent trafficking of GluA1-containing receptors. Phosphorylation at Ser831 by CaMKII and at Ser845 by PKA enhances insertion of GluA1-containing receptors into the postsynaptic membrane and can modulate channel conductance. The trafficking of GluA1 is also regulated by interactions with auxiliary subunits such as TARPs.

Calcium permeability: The calcium permeability of AMPA receptors depends on subunit composition. Receptors containing GluA2 edited at the Q/R site are calcium-impermeable; receptors lacking GluA2 (for example, GluA1-containing receptors without GluA2) are calcium-permeable.

Physiological and clinical significance: GluA1-dependent trafficking and signaling contribute to hippocampal long-term potentiation and learning and memory. Alterations in GluA1 function or expression have been linked to various conditions, including cognitive disorders, addiction, and mood disorders, and AMPA receptor–targeted strategies are explored in research and therapeutics.