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Presynaptic spinophilin tunes neurexin signalling to control active zone architecture and function.

MPG-Autoren
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Göttfert,  F.
Department of NanoBiophotonics, MPI for Biophysical Chemistry, Max Planck Society;

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Hell,  S. W.
Department of NanoBiophotonics, MPI for Biophysical Chemistry, Max Planck Society;

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Zitation

Muhammad, K., Reddy-Alla, S., Driller, J. H., Schreiner, D., Rey, U., Böhme, M. A., et al. (2015). Presynaptic spinophilin tunes neurexin signalling to control active zone architecture and function. Nature Communications, 6: 8362. doi:10.1038/ncomms9362.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-0029-1EE8-2
Zusammenfassung
Assembly and maturation of synapses at the Drosophila neuromuscular junction (NMJ) depend on trans-synaptic neurexin/neuroligin signalling, which is promoted by the scaffolding protein Syd-1 binding to neurexin. Here we report that the scaffold protein spinophilin binds to the C-terminal portion of neurexin and is needed to limit neurexin/neuroligin signalling by acting antagonistic to Syd-1. Loss of presynaptic spinophilin results in the formation of excess, but atypically small active zones. Neuroligin-1/neurexin-1/Syd-1 levels are increased at spinophilin mutant NMJs, and removal of single copies of the neurexin-1, Syd-1 or neuroligin-1 genes suppresses the spinophilin-active zone phenotype. Evoked transmission is strongly reduced at spinophilin terminals, owing to a severely reduced release probability at individual active zones. We conclude that presynaptic spinophilin fine-tunes neurexin/neuroligin signalling to control active zone number and functionality, thereby optimizing them for action potential-induced exocytosis.