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

Journal article

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: Owald, D; Khorramshahi, O; Gupta, V; Banovic, D; Depner, H

• Journal: Nature neuroscience
• Volume: 15
• Issue: 9
• Pages: 1219-1226
• Publication date: 2012-09-01
• DOI: 10.1038/nn.3183
• EISSN: 1546-1726
• ISSN: 1097-6256
• Language: English
• Keywords: Cell Adhesion Molecules, Neuronal; Neuromuscular Junction; Drosophila; Phosphoproteins; Immunoprecipitation; Caenorhabditis elegans; Immunohistochemistry; Saccharomyces cerevisiae; Cloning, Molecular; Synapses; Cell Adhesion Molecules; Drosophila Proteins; Animals; Receptors, Glutamate; PDZ Domains; Microscopy, Electron; GTPase-Activating Proteins; Presynaptic Terminals