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
  • Acetylcholine/pharmacology
  • Animals
  • Animals, Genetically Modified
  • Botulinum Toxins, Type A/metabolism
  • Green Fluorescent Proteins/genetics
  • Humans
  • In Vitro Techniques
  • Larva
  • Leucine/genetics
  • Locomotion/genetics
  • Miniature Postsynaptic Potentials/drug effects
  • Miniature Postsynaptic Potentials/genetics
  • Muscle, Skeletal/metabolism
  • Mutation/genetics*
  • Neuromuscular Junction/genetics*
  • Patch-Clamp Techniques
  • Phenotype
  • Proline/genetics
  • Receptors, Cholinergic/genetics*
  • Swimming/physiology
  • Zebrafish
PubMed
25080583 Full text @ J. Neurosci.
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
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping