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.
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Acknowledgements
We would like to thank C. Quentin and A. Stawrakakis for excellent technical assistance and R. Jahn for the use of equipment. T. Andlauer and U. Thomas critically read the manuscript. We further thank M. Bhat (University of North Carolina) and W. Xie (Southeast University, Nanjing) for generously sharing reagents. This work was supported by grants from the Deutsche Forschungsgemeinschaft to S.J.S. (Exc 257, SI849/2-1 and 2-2, TP A16/SFB 551, TP B23/SFB581, TP A3 and A6/SFB 958) and H.A. (AB 116/3-2). M.H. is funded by a European Research Council Starting Grant (Astrofunc).
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D.O., O.K. and S.J.S. designed research. D.O., O.K., V.K.G., D.B., H.D., W.F., C.W., S.M. and E.R. performed experiments. D.O., O.K., V.K.G., D.B., H.D., W.F., C.W., S.M., H.A. and S.J.S. analyzed data. M.H. and S.E. shared protocols, reagents and advice. All authors commented on the paper. D.O., O.K. and S.J.S. wrote the paper.
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Owald, D., Khorramshahi, O., Gupta, V. et al. Cooperation of Syd-1 with Neurexin synchronizes pre- with postsynaptic assembly. Nat Neurosci 15, 1219–1226 (2012). https://doi.org/10.1038/nn.3183
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DOI: https://doi.org/10.1038/nn.3183
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