Bm. Williams et al., The long internal loop of the alpha 3 subunit targets nAChRs to subdomainswithin individual synapses on neurons in vivo, NAT NEUROSC, 1(7), 1998, pp. 557-562
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.