Differences in the fate of neuronal acetylcholine receptor protein expressed in neurons and stably transfected cells.

Ligand-gated ion channels are structurally complex transmembrane proteins that all neurons must synthesize for rapid chemical synaptic transmission. The most abundant nicotinic acetylcholine receptor serving as a ligand-gated ion channel in the nervous system is a species that contains alpha7 subunits, binds alpha-bungarotoxin, and has a high relative permeability to calcium. The ability of neurons to make such receptors was compared with that of non-neuronal cells stably transfected with an alpha7 cDNA to determine whether neuron-specific machinery is likely to aid in their assembly or stabilization. Transfected cells expressed alpha7 protein and assembled it into a species that was indistinguishable in size and pharmacology from native receptors, but much of the alpha7 protein they synthesized was rapidly degraded without becoming receptor. Neurons were not only more efficient than the best transfectants at assembling the receptors but also produced a subpopulation of receptors on the cell surface that was relatively stable and resistant to solubilization. This subpopulation, which was absent from transfected cells, may be tethered to cytoskeletal elements in the neurons. The results support the contention that neurons contain components that facilitate the production and stabilization of ligand-gated ion channels.