Phosphoproteomic analysis supporting structural basis for GABAA receptor pi activation

GABAA receptors (GABAAR) are pentameric chloride channels comprising various combinations of different subunits that are activated by γ-aminobutyric acid (GABA), the main inhibitory neurotransmitter in vertebrates. we show here that GABRP chloride channel activity and ERK signaling is directly regulated by GABA binding to GABRP homopentamers. To help uncover GABRP’s link to ERK activity we used phosphoproteomic analysis to reveal signaling pathways regulated by GABA stimulation. Interestingly, and similar to metabotropic GABABRs, GABRP activation leads to phosphorylation of G-protein coupled pathways. These studies open new avenues for understanding GABRP signaling and additionally establish a foundation for conceptualizing the gating mechanism of related pentameric ligand gated ion channels. These studies open new avenues for understanding GABRP signaling and additionally establish a foundation for conceptualizing the gating mechanism of related pentameric ligand gated ion channels.