Abstract
The clustering and maintenance of nicotinic acetylcholine receptors (AChRs) at high density in the postsynaptic membrane is a hallmark of the mammalian neuromuscular junction (NMJ). The regulation of receptor density/turnover rate at synapses is one of the main thrusts of neurobiology because it plays an important role in synaptic development and synaptic plasticity. The state-of-the-art imaging revealed that AChRs are highly dynamic despite the overall structural stability of the NMJ over the lifetime of the animal. This review highlights the work on the metabolic stability of AChRs at developing and mature NMJs and discusses the role of synaptic activity and the regulatory signaling pathways involved in the dynamics of AChRs.
Highlights
The clustering and maintenance of nicotinic acetylcholine receptors (AChRs) at high density in the postsynaptic membrane is a hallmark of the mammalian neuromuscular junction (NMJ) [1,2,3]
These estimates were based on the assumption that once AChRs are internalized, they are targeted for degradation and did not consider the possibility that those receptors can continuously recycle back to the postsynaptic membrane with their BTX tag
The picture emerging from recent work is that nAChRs in the postsynaptic apparatus are highly dynamic despite the overall structural stability of the neuromuscular junction e (Figure 1)
Summary
The clustering and maintenance of nicotinic acetylcholine receptors (AChRs) at high density in the postsynaptic membrane is a hallmark of the mammalian neuromuscular junction (NMJ) [1,2,3]. When fluorescent or radiolabeled BTX was used as a ligand to monitor the turnover rate of receptors, the half-life was quite long (t 1 ≈ 9–14 days) at fully functioning synapses, and that this half-life was significantly reduced at surgically denervated synapses (t1/2 ≈ 1–3 days) or when synaptic activity was compromised by diseases [32,33,34,35,36] These estimates were based on the assumption that once AChRs are internalized, they are targeted for degradation (presumably in lysosomes) and did not consider the possibility that those receptors can continuously recycle back to the postsynaptic membrane with their BTX tag.
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