title: RIM-binding protein, a central part of the active zone, is essential for neurotransmitter release.
abstract: The molecular machinery mediating the fusion of synaptic vesicles (SVs) at presynaptic active zone (AZ) membranes has been studied in detail, and several essential components have been identified. AZ-associated protein scaffolds are viewed as only modulatory for transmission. We discovered that Drosophila Rab3-interacting molecule (RIM)-binding protein (DRBP) is essential not only for the integrity of the AZ scaffold but also for exocytotic neurotransmitter release. Two-color stimulated emission depletion microscopy showed that DRBP surrounds the central Ca(2+) channel field. In drbp mutants, Ca(2+) channel clustering and Ca(2+) influx were impaired, and synaptic release probability was drastically reduced. Our data identify RBP family proteins as prime effectors of the AZ scaffold that are essential for the coupling of SVs, Ca(2+) channels, and the SV fusion machinery.
authors.affiliation: Department of Genetics, Institute for Biology, Free University Berlin, 14195 Berlin, Germany.
authors.forename: Karen S Y
authors.initials: KS
authors.lastname: Liu
authors.forename: Matthias
authors.initials: M
authors.lastname: Siebert
authors.forename: Sara
authors.initials: S
authors.lastname: Mertel
authors.forename: Elena
authors.initials: E
authors.lastname: Knoche
authors.forename: Stephanie
authors.initials: S
authors.lastname: Wegener
authors.forename: Carolin
authors.initials: C
authors.lastname: Wichmann
authors.forename: Tanja
authors.initials: T
authors.lastname: Matkovic
authors.forename: Karzan
authors.initials: K
authors.lastname: Muhammad
authors.forename: Harald
authors.initials: H
authors.lastname: Depner
authors.forename: Christoph
authors.initials: C
authors.lastname: Mettke
authors.forename: Johanna
authors.initials: J
authors.lastname: Bückers
authors.forename: Stefan W
authors.initials: SW
authors.lastname: Hell
authors.forename: Martin
authors.initials: M
authors.lastname: Müller
authors.forename: Graeme W
authors.initials: GW
authors.lastname: Davis
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schmitz
authors.forename: Stephan J
authors.initials: SJ
authors.lastname: Sigrist
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D008297:Male; D009154:Mutation; D018377:Neurotransmitter Agents / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000502:physiology*; D013569:Synapses
chemical_list: D015220:Calcium Channels; D002352:Carrier Proteins; D029721:Drosophila Proteins; D018377:Neurotransmitter Agents