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Nat Commun. 2015 Oct 16;6:8362. doi: 10.1038/ncomms9362.

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

Author information

1
Freie Universität Berlin, Institute for Biology/Genetics, Takustrasse 6, Berlin 14195, Germany.
2
NeuroCure, Charité, Charitéplatz 1, Berlin 10117, Germany.
3
Freie Universität Berlin, Institut für Chemie und Biochemie /Strukturbiochmie, Takustrasse 6, Berlin D-14195, Germany.
4
Biozentrum, University of Basel, Klingelbergstrasse 50-70, Basel 4056, Switzerland.
5
Leibniz Institut für Molekulare Pharmakologie, Robert-Roessle-Strasse 10, Berlin 13125, Germany.
6
Department of NanoBiophotonics, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, Göttingen 37077, Germany.
7
VIB Center for the Biology of Disease, Herestraat 49, Leuven 3000, Belgium.

Abstract

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.

PMID:
26471740
PMCID:
PMC4633989
DOI:
10.1038/ncomms9362
[Indexed for MEDLINE]
Free PMC Article

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