Paralytic zebrafish lacking acetylcholine receptors fail to localize rapsyn clusters to the synapse.
Physiological analysis of two lines of paralytic mutant zebrafish, relaxed and sofa potato, reveals defects in distinct types of receptors in skeletal muscle. In sofa potato the paralysis results from failed synaptic transmission because of the absence of acetylcholine receptors, whereas relaxed mutants lack dihydropyridine receptor-mediated release of internal calcium in response to the muscle action potential. Synaptic structure and function appear normal in relaxed, showing that muscle paralysis per se does not impede proper synapse development. However, sofa potato mutants show incomplete development of the postsynaptic complex. Specifically, in the absence of ACh receptors, clusters of the receptor-aggregating protein rapsyn form in the extrasynaptic membrane but generally fail to localize to the subsynaptic region. Our results indicate that, although rapsyn molecules are capable of self-aggregation, interaction with ACh receptors is required for proper subsynaptic localization.
Ono
F
F
Department of Neurobiology and Behavior, State University of New York at Stony Brook, Stony Brook, New York 11794, USA. fono@notes.cc.sunysb.edu
Higashijima
S
S
Shcherbatko
A
A
Fetcho
J R
JR
Brehm
P
P
D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D004558:Electric Stimulation; D005456:Fluorescent Dyes; D049452:Green Fluorescent Proteins; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009119:Muscle Contraction / Q000187:drug effects; D009124:Muscle Proteins / Q000378:metabolism*; D009154:Mutation; D010243:Paralysis / Q000503:physiopathology*; D018408:Patch-Clamp Techniques; D021381:Protein Transport / Q000502:physiology; D011940:Receptor Aggregation / Q000502:physiology; D011950:Receptors, Cholinergic / Q000172:deficiency* / Q000235:genetics; D013116:Spinal Cord / Q000503:physiopathology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009435:Synaptic Transmission / Q000187:drug effects; D015027:Zebrafish
D002038:Bungarotoxins; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D005456:Fluorescent Dyes; D008164:Luminescent Proteins; D009124:Muscle Proteins; D011950:Receptors, Cholinergic; C051609:peripheral membrane protein 43K; D049452:Green Fluorescent Proteins; D002110:Caffeine; D000109:Acetylcholine