title: Cooperation of Syd-1 with Neurexin synchronizes pre- with postsynaptic assembly.
abstract: Synapse formation and maturation requires bidirectional communication across the synaptic cleft. The trans-synaptic Neurexin-Neuroligin complex can bridge this cleft, and severe synapse assembly deficits are found in Drosophila melanogaster neuroligin (Nlg1, dnlg1) and neurexin (Nrx-1, dnrx) mutants. We show that the presynaptic active zone protein Syd-1 interacts with Nrx-1 to control synapse formation at the Drosophila neuromuscular junction. Mutants in Syd-1 (RhoGAP100F, dsyd-1), Nrx-1 and Nlg1 shared active zone cytomatrix defects, which were nonadditive. Syd-1 and Nrx-1 formed a complex in vivo, and Syd-1 was important for synaptic clustering and immobilization of Nrx-1. Consequently, postsynaptic clustering of Nlg1 was affected in Syd-1 mutants, and in vivo glutamate receptor incorporation was changed in Syd-1, Nrx-1 and Nlg1 mutants. Stabilization of nascent Syd-1-Liprin-α (DLiprin-α) clusters, important to initialize active zone formation, was Nlg1 dependent. Thus, cooperation between Syd-1 and Nrx-1-Nlg1 seems to orchestrate early assembly processes between pre- and postsynaptic membranes, promoting avidity of newly forming synaptic scaffolds.
authors.affiliation: Freie Universität Berlin, Institute for Biology/Genetics, Berlin, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Owald
authors.forename: Omid
authors.initials: O
authors.lastname: Khorramshahi
authors.forename: Varun K
authors.initials: VK
authors.lastname: Gupta
authors.forename: Daniel
authors.initials: D
authors.lastname: Banovic
authors.forename: Harald
authors.initials: H
authors.lastname: Depner
authors.forename: Wernher
authors.initials: W
authors.lastname: Fouquet
authors.forename: Carolin
authors.initials: C
authors.lastname: Wichmann
authors.forename: Sara
authors.initials: S
authors.lastname: Mertel
authors.forename: Stefan
authors.initials: S
authors.lastname: Eimer
authors.forename: Eric
authors.initials: E
authors.lastname: Reynolds
authors.forename: Matthew
authors.initials: M
authors.lastname: Holt
authors.forename: Hermann
authors.initials: H
authors.lastname: Aberle
authors.forename: Stephan J
authors.initials: SJ
authors.lastname: Sigrist
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D015815:Cell Adhesion Molecules / Q000502:physiology; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000502:physiology*; D003001:Cloning, Molecular; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins; D008854:Microscopy, Electron; D009469:Neuromuscular Junction / Q000502:physiology; D054731:PDZ Domains / Q000235:genetics; D010750:Phosphoproteins / Q000378:metabolism; D017729:Presynaptic Terminals / Q000502:physiology*; D017470:Receptors, Glutamate / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics; D013569:Synapses / Q000502:physiology*
chemical_list: D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D029721:Drosophila Proteins; D020690:GTPase-Activating Proteins; D047908:Intracellular Signaling Peptides and Proteins; C490600:Liprin-alpha protein, Drosophila; C491321:Nrx protein, Drosophila; D010750:Phosphoproteins; D017470:Receptors, Glutamate; C548043:RhoGAP100F protein, Drosophila