Structure and function of nicotinic receptors

Abstract

The neuronal nicotinic acetylcholine receptor gene family encodes proteins that form either homo­oligomeric or hetero-oligomeric ligand gated ion channels. Although the total number of combinations of possible receptors is large, only a few have been demonstrated to function in the oocyte expression system. However, those that have been expressed differ from each other in several important ways. Receptors expressed in oocytes differ with respect to the ligands that activate them, their single channel properties, their permselectivity, and their modulation by external calcium. Furthermore, some cells express several of the genes that encode these receptor subunits and assemble receptors that contain a subset of the expressed genes. There are, therefore, probably mechanisms responsible for the assembly and targeting of receptors containing specific combinations of subunits. We investigated this possibility initially focussing on the homo-oligomeric alpha7 receptor and identified a requirement for the activity of a peptidyl prolyl isomerase in the assembly of this receptor. This requirement is shared by the serotonin-gated ion channel. We have created a number of mutations in the alpha 7 protein to try to identify relevant proline residues and have examined the expression of these mutant receptors in the Xenopus oocyte expression system.