Acetylcholine negatively regulates development of the neuromuscular junction through distinct cellular mechanisms.
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An MC, Lin W, Yang J, Dominguez B, Padgett D, Sugiura Y, Aryal P, Gould TW, Oppenheim RW, Hester ME, Kaspar BK, Ko CP, Lee KF
Acetylcholine negatively regulates development of the neuromuscular junction through distinct cellular mechanisms.
Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10702-7. doi: 10.1073/pnas.1004956107. Epub 2010 May 24.
- PubMed ID
- 20498043 [ View in PubMed]
- Abstract
Emerging evidence suggests that the neurotransmitter acetylcholine (ACh) negatively regulates the development of the neuromuscular junction, but it is not clear if ACh exerts its effects exclusively through muscle ACh receptors (AChRs). Here, we used genetic methods to remove AChRs selectively from muscle. Similar to the effects of blocking ACh biosynthesis, eliminating postsynaptic AChRs increased motor axon branching and expanded innervation territory, suggesting that ACh negatively regulates synaptic growth through postsynaptic AChRs. However, in contrast to the effects of blocking ACh biosynthesis, eliminating postsynaptic AChRs in agrin-deficient mice failed to restore deficits in pre- and postsynaptic differentiation, suggesting that ACh negatively regulates synaptic differentiation through nonpostsynaptic receptors. Consistent with this idea, the ACh agonist carbachol inhibited presynaptic specialization of motorneurons in vitro. Together, these data suggest that ACh negatively regulates axon growth and presynaptic specialization at the neuromuscular junction through distinct cellular mechanisms.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Carbamoylcholine Neuronal acetylcholine receptor subunit alpha-2 Protein Humans YesAgonistDetails