The long internal loop of the alpha 3 subunit targets nAChRs to subdomainswithin individual synapses on neurons in vivo

Different types of neurotransmitter receptors coexist within single neurons and must be targeted to discrete synaptic regions for proper function. In chick ciliary ganglion neurons, nicotinic acetylcholine receptors (nAChRs) containing alpha 3 and alpha 5 subunits are concentrated in the postsynapti c membrane, whereas alpha-bungarotoxin receptors composed of alpha 7 subuni ts are localized perisynaptically and excluded from the synapse. Using retr oviral vector-mediated gene transfer in vivo, we show that the long cytopla smic loop of alpha 3 targets chimeric alpha 7 subunits to the synapse and r educes endogenous nAChR surface levels, whereas the alpha 5 loop does neith er. These results show that a particular domain of one subunit targets spec ific receptor subtypes to the interneuronal synapse in vivo. Moreover, our findings suggest a difference in the mechanisms that govern assembly of int erneuronal synapses as compared to the neuromuscular junction in vertebrate s.