PUBLICATION
A Single Mutation in the Acetylcholine Receptor δ-Subunit Causes Distinct Effects in Two Types of Neuromuscular Synapses
- Authors
- Park, J.Y., Mott, M., Williams, T., Ikeda, H., Wen, H., Linhoff, M., Ono, F.
- ID
- ZDB-PUB-140801-1
- Date
- 2014
- Source
- The Journal of neuroscience : the official journal of the Society for Neuroscience 34: 10211-10218 (Journal)
- Registered Authors
- Ono, Fumihito, Park, Jee-Young
- Keywords
- acetylcholine receptors, neuromuscular diseases, zebrafish
- MeSH Terms
-
- Patch-Clamp Techniques
- Locomotion/genetics
- Animals, Genetically Modified
- Swimming/physiology
- Green Fluorescent Proteins/genetics
- Animals
- Miniature Postsynaptic Potentials/drug effects
- Miniature Postsynaptic Potentials/genetics
- Mutation/genetics*
- Acetylcholine/pharmacology
- Leucine/genetics
- In Vitro Techniques
- Phenotype
- Botulinum Toxins, Type A/metabolism
- Zebrafish
- Humans
- Neuromuscular Junction/genetics*
- Larva
- Muscle, Skeletal/metabolism
- Proline/genetics
- Receptors, Cholinergic/genetics*
- PubMed
- 25080583 Full text @ J. Neurosci.
Citation
Park, J.Y., Mott, M., Williams, T., Ikeda, H., Wen, H., Linhoff, M., Ono, F. (2014) A Single Mutation in the Acetylcholine Receptor δ-Subunit Causes Distinct Effects in Two Types of Neuromuscular Synapses. The Journal of neuroscience : the official journal of the Society for Neuroscience. 34:10211-10218.
Abstract
Mutations in AChR subunits, expressed as pentamers in neuromuscular junctions (NMJs), cause various types of congenital myasthenic syndromes. In AChR pentamers, the adult ε subunit gradually replaces the embryonic γ subunit as the animal develops. Because of this switch in subunit composition, mutations in specific subunits result in synaptic phenotypes that change with developmental age. However, a mutation in any AChR subunit is considered to affect the NMJs of all muscle fibers equally. Here, we report a zebrafish mutant of the AChR δ subunit that exhibits two distinct NMJ phenotypes specific to two muscle fiber types: slow or fast. Homozygous fish harboring a point mutation in the δ subunit form functional AChRs in slow muscles, whereas receptors in fast muscles are nonfunctional. To test the hypothesis that different subunit compositions in slow and fast muscles underlie distinct phenotypes, we examined the presence of ε/γ subunits in NMJs using specific antibodies. Both wild-type and mutant larvae lacked ε/γ subunits in slow muscle synapses. These findings in zebrafish suggest that some mutations in human congenital myasthenic syndromes may affect slow and fast muscle fibers differently.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping