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- Title
Cooperation of Syd-1 with Neurexin synchronizes pre- with postsynaptic assembly.
- Authors
Owald, David; Khorramshahi, Omid; Gupta, Varun K; Banovic, Daniel; Depner, Harald; Fouquet, Wernher; Wichmann, Carolin; Mertel, Sara; Eimer, Stefan; Reynolds, Eric; Holt, Matthew; Aberle, Hermann; Sigrist, Stephan J
- 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-? (DLiprin-?) 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.
- Subjects
NEUREXINS; POSTSYNAPTIC density protein; DROSOPHILA melanogaster; NEUROMUSCULAR diseases; GLUTAMATE receptors
- Publication
Nature Neuroscience, 2012, Vol 15, Issue 9, p1219
- ISSN
1097-6256
- Publication type
Article
- DOI
10.1038/nn.3183