Acetylcholine negatively regulates development of the neuromuscular junction through distinct cellular mechanisms
| Autor: | Bertha Dominguez, Brian K. Kaspar, Ronald W. Oppenheim, Yoshie Sugiura, Prafulla Aryal, Thomas W. Gould, Weichun Lin, Kuo-Fen Lee, Mark E. Hester, Mahru C. An, Chien-Ping Ko, Jiefei Yang, Daniel Padgett |
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| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_specialty
animal structures Neuromuscular Junction Cholinergic Agonists Receptors Nicotinic Biology Neuromuscular junction Mice chemistry.chemical_compound Postsynaptic potential Internal medicine medicine Animals Neurotransmitter Receptor Acetylcholine receptor Multidisciplinary Acetylation Cell Differentiation Biological Sciences Acetylcholine Cell biology medicine.anatomical_structure Endocrinology chemistry Cholinergic Carbachol Postsynaptic density medicine.drug |
| Zdroj: | Proceedings of the National Academy of Sciences. 107:10702-10707 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1004956107 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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