Cooperation of Syd-1 with Neurexin synchronizes pre- with postsynaptic assembly

Nat Neurosci. 2012 Sep;15(9):1219-26. doi: 10.1038/nn.3183. Epub 2012 Aug 5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans
  • Cell Adhesion Molecules / physiology
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / physiology*
  • Cloning, Molecular
  • Drosophila
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila Proteins / physiology*
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / physiology*
  • Immunohistochemistry
  • Immunoprecipitation
  • Intracellular Signaling Peptides and Proteins
  • Microscopy, Electron
  • Neuromuscular Junction / physiology
  • PDZ Domains / genetics
  • Phosphoproteins / metabolism
  • Presynaptic Terminals / physiology*
  • Receptors, Glutamate / physiology
  • Saccharomyces cerevisiae / genetics
  • Synapses / physiology*


  • Cell Adhesion Molecules
  • Cell Adhesion Molecules, Neuronal
  • Drosophila Proteins
  • GTPase-Activating Proteins
  • Intracellular Signaling Peptides and Proteins
  • Liprin-alpha protein, Drosophila
  • Nrx protein, Drosophila
  • Phosphoproteins
  • Receptors, Glutamate
  • RhoGAP100F protein, Drosophila