GABA A (γ-aminobutyric acid-type A) receptors are members of the cysteine-loop family of neurotransmitter-gated ion channels. GABA binding to A-type receptors induces anion-selective ion channel opening. These receptors are the principal fast inhibitory neurotransmitter receptors in the CNS. GABA A receptors are heteropentamer combinations of seven subunit types; α, β, γ, δ, ε, θ, and π. Three subunits, α, β, and γ, have at least three separate gene products in mammals, and typical GABA A receptors have some combination of α, β, and γ subunits.
The rat γ2 isoform is a 48 kDa, 436 amino acid (aa), 4 transmembrane protein with two terminal extracellular regions. The ligand-binding region is in the N-terminus (aa 30 - 233). The γ2 subunit is part of the most common GABA A receptor combination in the mammalian brain (α1β2γ2). GABA binds at α-β interfaces, while benzodiazepine binds to alpha- gamma interfaces. There are two γ2 splice forms, the longest contains a consensus phosphorylation site in the second cytoplasmic domain, and a short form that shows an absence of this site through a deletion of aa 376 - 383. PKC phosphorylates the long form at S381, while both the short and long forms are phosphorylated at S365. Phosphorylation blocks receptor activity. The γ2 subunits are also palmitoylated at multiple sites on cysteines that lay between aa 415 - 461, facilitating membrane trafficking.
