GRIA6

GRIA6 (glutamate receptor, ionotropic, AMPA type subunit 6) is a gene that encodes the GluA6 subunit of AMPA-type ionotropic glutamate receptors. AMPA receptors mediate fast excitatory synaptic transmission in the vertebrate central nervous system. Subunits assemble as tetrameric receptors and can form homo- or heteromeric complexes with other GRIA family members, contributing to the diversity of receptor properties in different neurons. GRIA6 is expressed in the brain, with transcripts detected in cortex and hippocampus among other regions; expression patterns can vary during development and between neuronal populations.

The GluA6 protein is predicted to have the typical AMPA receptor architecture, including an extracellular N-terminus, a ligand-binding domain, four transmembrane segments (M1–M4), and an intracellular C-terminus. As with other AMPA receptor subunits, GRIA6 transcripts can undergo RNA editing and alternative splicing, which modulate receptor kinetics, ion permeability, and trafficking. The flip/flop alternative splicing affects channel kinetics, while editing at certain sites can influence calcium permeability and pharmacology, though the precise impact of GRIA6-specific editing is an area of study.

Physiological roles include participation in fast excitatory synaptic transmission and synaptic plasticity. Receptors containing GRIA6 can assemble with other GRIA subunits and interact with auxiliary proteins such as TARPs and scaffolding proteins to regulate trafficking, localization, and gating at synapses.

Clinical and research interest in GRIA6 focuses on its potential involvement in epilepsy, neurodevelopmental and psychiatric disorders, and cognitive function, but associations are not yet definitive and require further study.