PUBLICATION

The zebrafish motility mutant twitch once reveals new roles for rapsyn in synaptic function

Authors
Ono, F., Shcherbatko, A., Higashijima, S.-I., Mandel, G., and Brehm, P.
ID
ZDB-PUB-020807-13
Date
2002
Source
The Journal of neuroscience : the official journal of the Society for Neuroscience   22(15): 6491-6498 (Journal)
Registered Authors
Higashijima, Shin-ichi
Keywords
tetratricopeptide repeats; synaptic depression; myasthenia gravis; synapse development; muscle fatigue; rapsyn
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Behavior, Animal/physiology
  • Electric Stimulation
  • Escape Reaction/physiology
  • Green Fluorescent Proteins
  • Homozygote
  • In Vitro Techniques
  • Luminescent Proteins/genetics
  • Membrane Potentials/physiology
  • Motor Endplate/physiology
  • Muscle Fatigue/genetics
  • Muscle Fatigue/physiology
  • Muscle Proteins/genetics
  • Muscle Proteins/physiology*
  • Muscle, Skeletal/innervation
  • Muscle, Skeletal/metabolism
  • Patch-Clamp Techniques
  • Receptor Aggregation/physiology
  • Receptors, Cholinergic/metabolism
  • Recombinant Fusion Proteins/genetics
  • Recombinant Fusion Proteins/metabolism
  • Repetitive Sequences, Amino Acid/genetics
  • Synapses/physiology*
  • Zebrafish
PubMed
12151528 Full text @ J. Neurosci.
Abstract
Upon touch, twitch once zebrafish respond with one or two swimming strokes instead of typical full-blown escapes. This use-dependent fatigue is shown to be a consequence of a mutation in the tetratricopeptide domain of muscle rapsyn, inhibiting formation of subsynaptic acetylcholine receptor clusters. Physiological analysis indicates that reduced synaptic strength, attributable to loss of receptors, is augmented by a potent postsynaptic depression not seen at normal neuromuscular junctions. The synergism between these two physiological processes is causal to the use-dependent muscle fatigue. These findings offer insights into the physiological basis of human myasthenic syndrome and reveal the first demonstration of a role for rapsyn in regulating synaptic function.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping