Regulation of GABAARs by Transmembrane Accessory Proteins

Abstract

The vast majority of fast inhibitory transmission in the brain is mediated by GABA acting on GABA_A receptors (GABA_ARs), which provides inhibitory balance to excitatory drive and controls neuronal output. GABA_ARs are also effectively targeted by clinically important drugs for treatment in a number of neurological disorders. It has long been hypothesized that function and pharmacology of GABA_ARs are determined by the channel pore-forming subunits. However, recent studies have provided new dimensions in studying GABA_ARs due to several transmembrane proteins that interact with GABA_ARs and modulate their trafficking and function. In this review, we summarize recent findings on these novel GABA_AR transmembrane regulators and highlight a potential avenue to develop new GABA_AR psychopharmacology by targeting these receptor-associated membrane proteins.

Keywords: Clptm1; GABA(A) receptor; GARLH4; Lhfpl4; Shisa7; auxiliary subunit; benzodiazepines.