The ligand-gated ion channel superfamily plays a critical role in neuronal excitability. The
functions of glycine receptor (GlyR) and nicotinic acetylcholine receptor are modulated by G
protein βγ subunits. The molecular determinants for this functional modulation, however, are
still unknown. Studying mutant receptors, we identified two basic amino acid motifs within
the large intracellular loop of the GlyR α 1 subunit that are critical for binding and functional
modulation by Gβγ. Mutations within these sequences demonstrated that all of the residues …