title: Evidence that cysteine string proteins regulate an early step in the Ca2+-dependent secretion of neurotransmitter at Drosophila neuromuscular junctions.
abstract: Previous work indicated that the temperature-dependent block of synaptic transmission in cysteine string protein (csp) mutants of Drosophila was attributable to a failure of nerve impulses to trigger transmitter release. The current investigations were undertaken to resolve in more detail the mechanism of this transmission deficit. Our studies reveal that the spider venom toxin alpha-latrotoxin can trigger a sustained discharge of quanta at neuromuscular junctions of csp mutant larvae at nonpermissive temperature. The same is true of the calcium ionophore ionomycin. However, solutions with an elevated concentration of K or Ca ions fail to circumvent the block of quantal secretion in these mutants. Likewise, 4-aminopyridine, which augments transmitter release at permissive temperature in csp mutants, fails to reverse the inhibition of impulse-evoked transmitter release at elevated temperature. These data are consistent with the hypothesis that there is a deficit either in Ca ion entry or in the ability of Ca ions to trigger exocytosis in csp mutants at nonpermissive temperatures. In part, because of previous work showing that csps are important for the functional expression of N-type Ca channels in frog oocytes, we favor the idea that csps participate in a regulatory interaction involving presynaptic Ca channels.
authors.affiliation: Department of Molecular and Medical Pharmacology and The Crump Institute for Biological Imaging, University of California at Los Angeles School of Medicine, Los Angeles, California 90095, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Umbach
authors.forename: C B
authors.initials: CB
authors.lastname: Gundersen
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D004330:Drosophila / Q000235:genetics / Q000378:metabolism*; D004594:Electrophysiology; D050956:HSP40 Heat-Shock Proteins; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008565:Membrane Proteins; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009469:Neuromuscular Junction / Q000378:metabolism* / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D013111:Spider Venoms / Q000494:pharmacology; D013696:Temperature
chemical_list: D050956:HSP40 Heat-Shock Proteins; D007476:Ionophores; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D013111:Spider Venoms; C088460:cysteine string protein; D015759:Ionomycin; C020763:alpha-latrotoxin; D015761:4-Aminopyridine; D011188:Potassium; D002118:Calcium