Presynaptic dysfunction in Drosophila csp mutants.
Cysteine string proteins are synapse-specific proteins. In Drosophila, csp deletion mutants exhibit temperature-sensitive paralysis and early death. Here, we report that neuromuscular transmission is impaired presynaptically in these csp mutant larvae. At 22 degrees C, evoked transmitter release is depressed relative to wild type and rescued controls, and high frequency stimulation of the nerve leads to sporadic failures. At 30 degrees C, stimulus-evoked responses decline gradually before failing completely. When the temperature is returned to 22 degrees C, evoked responses recover. Spontaneous release events persist at both 22 degrees C and 30 degrees C. Since nerve conduction and postsynaptic sensitivity are unaffected, these data indicate that csp mutations disrupt depolarization-secretion coupling. This disruption explains the cellular basis of the temperature-sensitive paralysis of these organisms.
Umbach
J A
JA
Department of Molecular and Medical Pharmacology School of Medicine, University of California, Los Angeles 90024.
Zinsmaier
K E
KE
Eberle
K K
KK
Buchner
E
E
Benzer
S
S
Gundersen
C B
CB
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004330:Drosophila / Q000235:genetics / Q000502:physiology*; D005071:Evoked Potentials / Q000187:drug effects; D017353:Gene Deletion; D050956:HSP40 Heat-Shock Proteins; D007814:Larva / Q000502:physiology; D008565:Membrane Proteins; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D009469:Neuromuscular Junction / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D013570:Synaptic Membranes / Q000502:physiology; D009435:Synaptic Transmission; D013696:Temperature
D050956:HSP40 Heat-Shock Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C088460:cysteine string protein; D002118:Calcium