Glycine Receptor Activation: When Three Out of Five Is Enough

The prototypic member of the acetylcholine receptor family, the muscle nicotinic receptor, is a heteromeric complex with five subunits but only two ligand-binding sites. However, some members of this receptor superfamily are homomeric, containing five seemingly identical binding sites. Whether activation actually requires binding of five agonist molecules in this situation is unclear. Such questions cannot be answered using classical pharmacological methods. Thus Beato et al. analyzed the single-channel activity of recombinant glycine receptors containing five 1 subunits, the principal juvenile form of this inhibitory synaptic receptor. The channels opened more efficaciously as the glycine concentration increased, but gating saturated when three glycine molecules were bound. They could not resolve whether the fourth and fifth bindings occur or are silent. The three out of five odds may be a general rule, because similar results have been suggested for homomeric GABAC and 5-HT3 channels. ΠDevelopment/Plasticity/Repair The Mouse Repulsive Guidance Molecule (RGM) Family