The Zebrafish motility mutant twitch once reveals new roles for rapsyn in synaptic function.
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.
Ono
Fumihito
F
Department of Neurobiology and Behavior, State University of New York at Stony Brook, Stony Brook, New York 11794, USA.
Shcherbatko
Anatoly
A
Higashijima
Shin-ichi
S
Mandel
Gail
G
Brehm
Paul
P
D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal / Q000502:physiology; D004558:Electric Stimulation; D004924:Escape Reaction / Q000502:physiology; D049452:Green Fluorescent Proteins; D006720:Homozygote; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000235:genetics; D008564:Membrane Potentials / Q000502:physiology; D009045:Motor Endplate / Q000502:physiology; D018763:Muscle Fatigue / Q000235:genetics / Q000502:physiology; D009124:Muscle Proteins / Q000235:genetics / Q000502:physiology*; D018482:Muscle, Skeletal / Q000294:innervation / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011940:Receptor Aggregation / Q000502:physiology; D011950:Receptors, Cholinergic / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid / Q000235:genetics; D013569:Synapses / Q000502:physiology*; D015027:Zebrafish
D008164:Luminescent Proteins; D009124:Muscle Proteins; D011950:Receptors, Cholinergic; D011993:Recombinant Fusion Proteins; C051609:peripheral membrane protein 43K; D049452:Green Fluorescent Proteins