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Development/Plasticity/Repair Identification of Nicotinic Acetylcholine Receptor Recycling

Summary: Development/Plasticity/Repair
Identification of Nicotinic Acetylcholine Receptor Recycling
and Its Role in Maintaining Receptor Density at the
Neuromuscular Junction In Vivo
Emile Bruneau,* David Sutter,* Richard I. Hume, and Mohammed Akaaboune
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109
In the CNS, receptor recycling is critical for synaptic plasticity; however, the recycling of receptors has never been observed at peripheral
synapses. Using a novel imaging technique, we show here that nicotinic acetylcholine receptors (AChRs) recycle into the postsynaptic
membrane of the neuromuscular junction. By sequentially labeling AChRs with biotin­bungarotoxin and streptavidin­fluorophore
conjugates, we were able to distinguish recycled, preexisting, and new receptor pools at synapses in living mice. Time-lapse imaging
revealed that recycled AChRs were incorporated into the synapse within hours of initial labeling, and their numbers increased with time.
At fully functional synapses, AChR recycling was robust and comparable in magnitude with the insertion of newly synthesized receptors,
whereas chronic synaptic activity blockade nearly abolished receptor recycling. Finally, using the same sequential labeling method, we
found that acetylcholinesterase, another synaptic component, does not recycle. These results identify an activity-dependent AChR-
recycling mechanism that enables the regulation of receptor density, which could lead to rapid alterations in synaptic efficacy.
Key words: toxin; turnover; synaptic transmission; neuromuscular junction; trafficking; acetylcholine receptor (AChR)
The density of neurotransmitter receptors is an important pa-
rameter in regulating the efficacy of synaptic transmission. In
both the central (O'Brien et al., 1998; Carroll et al., 1999a) and


Source: Alford, Simon - Department of Biological Sciences, University of Illinois at Chicago


Collections: Biology and Medicine