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Nat Commun. 2015 Sep 24;6:8302. doi: 10.1038/ncomms9302.

Wnt signalling tunes neurotransmitter release by directly targeting Synaptotagmin-1.

Author information

1
Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
2
Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, UK.

Abstract

The functional assembly of the synaptic release machinery is well understood; however, how signalling factors modulate this process remains unknown. Recent studies suggest that Wnts play a role in presynaptic function. To examine the mechanisms involved, we investigated the interaction of release machinery proteins with Dishevelled-1 (Dvl1), a scaffold protein that determines the cellular locale of Wnt action. Here we show that Dvl1 directly interacts with Synaptotagmin-1 (Syt-1) and indirectly with the SNARE proteins SNAP25 and Syntaxin (Stx-1). Importantly, the interaction of Dvl1 with Syt-1, which is regulated by Wnts, modulates neurotransmitter release. Moreover, presynaptic terminals from Wnt signalling-deficient mice exhibit reduced release probability and are unable to sustain high-frequency release. Consistently, the readily releasable pool size and formation of SNARE complexes are reduced. Our studies demonstrate that Wnt signalling tunes neurotransmitter release and identify Syt-1 as a target for modulation by secreted signalling proteins.

PMID:
26400647
PMCID:
PMC4667432
DOI:
10.1038/ncomms9302
[Indexed for MEDLINE]
Free PMC Article

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