title: A Syd-1 homologue regulates pre- and postsynaptic maturation in Drosophila.
abstract: Active zones (AZs) are presynaptic membrane domains mediating synaptic vesicle fusion opposite postsynaptic densities (PSDs). At the Drosophila neuromuscular junction, the ELKS family member Bruchpilot (BRP) is essential for dense body formation and functional maturation of AZs. Using a proteomics approach, we identified Drosophila Syd-1 (DSyd-1) as a BRP binding partner. In vivo imaging shows that DSyd-1 arrives early at nascent AZs together with DLiprin-alpha, and both proteins localize to the AZ edge as the AZ matures. Mutants in dsyd-1 form smaller terminals with fewer release sites, and release less neurotransmitter. The remaining AZs are often large and misshapen, and ectopic, electron-dense accumulations of BRP form in boutons and axons. Furthermore, glutamate receptor content at PSDs increases because of excessive DGluRIIA accumulation. The AZ protein DSyd-1 is needed to properly localize DLiprin-alpha at AZs, and seems to control effective nucleation of newly forming AZs together with DLiprin-alpha. DSyd-1 also organizes trans-synaptic signaling to control maturation of PSD composition independently of DLiprin-alpha.
authors.affiliation: Department of Genetics, Institute for Biology, Freie Universität Berlin, 14195 Berlin, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Owald
authors.forename: Wernher
authors.initials: W
authors.lastname: Fouquet
authors.forename: Manuela
authors.initials: M
authors.lastname: Schmidt
authors.forename: Carolin
authors.initials: C
authors.lastname: Wichmann
authors.forename: Sara
authors.initials: S
authors.lastname: Mertel
authors.forename: Harald
authors.initials: H
authors.lastname: Depner
authors.forename: Frauke
authors.initials: F
authors.lastname: Christiansen
authors.forename: Christina
authors.initials: C
authors.lastname: Zube
authors.forename: Christine
authors.initials: C
authors.lastname: Quentin
authors.forename: Jorg
authors.initials: J
authors.lastname: Körner
authors.forename: Henning
authors.initials: H
authors.lastname: Urlaub
authors.forename: Karl
authors.initials: K
authors.lastname: Mechtler
authors.forename: Stephan J
authors.initials: SJ
authors.lastname: Sigrist
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000378:metabolism* / Q000648:ultrastructure; D004625:Embryo, Nonmammalian / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D008124:Locomotion / Q000502:physiology; D008136:Longevity / Q000502:physiology; D009154:Mutation / Q000235:genetics; D009469:Neuromuscular Junction / Q000378:metabolism / Q000648:ultrastructure; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D011485:Protein Binding; D021381:Protein Transport; D040901:Proteomics; D017470:Receptors, Glutamate / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D055366:Synaptic Potentials
chemical_list: C510146:BRP protein, Drosophila; D029721:Drosophila Proteins; D020690:GTPase-Activating Proteins; D047908:Intracellular Signaling Peptides and Proteins; C490600:Liprin-alpha protein, Drosophila; D010750:Phosphoproteins; D017470:Receptors, Glutamate; C548043:RhoGAP100F protein, Drosophila