title: Drosophila CAPS is an essential gene that regulates dense-core vesicle release and synaptic vesicle fusion.
abstract: Calcium-activated protein for secretion (CAPS) is proposed to play an essential role in Ca2+-regulated dense-core vesicle exocytosis in vertebrate neuroendocrine cells. Here we report the cloning, mutation, and characterization of the Drosophila ortholog (dCAPS). Null dCAPS mutants display locomotory deficits and complete embryonic lethality. The mutant NMJ reveals a 50% loss in evoked glutamatergic transmission, and an accumulation of synaptic vesicles at active zones. Importantly, dCAPS mutants display a highly specific 3-fold accumulation of dense-core vesicles in synaptic terminals, which was not observed in mutants that completely arrest synaptic vesicle exocytosis. Targeted transgenic CAPS expression in identified motoneurons fails to rescue dCAPS neurotransmission defects, demonstrating a cell nonautonomous role in synaptic vesicle fusion. We conclude that dCAPS is required for dense-core vesicle release and that a dCAPS-dependent mechanism modulates synaptic vesicle release at glutamatergic synapses.
authors.affiliation: Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, UT 84112, USA.
authors.forename: R
authors.initials: R
authors.lastname: Renden
authors.forename: B
authors.initials: B
authors.lastname: Berwin
authors.forename: W
authors.initials: W
authors.lastname: Davis
authors.forename: K
authors.initials: K
authors.lastname: Ann
authors.forename: C T
authors.initials: CT
authors.lastname: Chin
authors.forename: R
authors.initials: R
authors.lastname: Kreber
authors.forename: B
authors.initials: B
authors.lastname: Ganetzky
authors.forename: T F
authors.initials: TF
authors.lastname: Martin
authors.forename: K
authors.initials: K
authors.lastname: Broadie
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000502:physiology; D005089:Exocytosis; D020043:Genes, Essential; D018698:Glutamic Acid / Q000502:physiology; D008561:Membrane Fusion / Q000502:physiology; D008969:Molecular Sequence Data; D009043:Motor Activity; D009046:Motor Neurons / Q000502:physiology; D009469:Neuromuscular Junction / Q000502:physiology; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D009435:Synaptic Transmission / Q000502:physiology; D013572:Synaptic Vesicles / Q000502:physiology*; D033921:Vesicular Transport Proteins
chemical_list: C409027:CADPS protein, human; D002135:Calcium-Binding Proteins; D033921:Vesicular Transport Proteins; D018698:Glutamic Acid