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Wnt signalling tunes neurotransmitter release by directly targeting Synaptotagmin-1

Author

Listed:
  • Lorenza Ciani

    (University College London)

  • Aude Marzo

    (University College London)

  • Kieran Boyle

    (University College London)

  • Eleanna Stamatakou

    (University College London)

  • Douglas M. Lopes

    (University College London)

  • Derek Anane

    (University College London)

  • Faye McLeod

    (University College London)

  • Silvana B. Rosso

    (University College London)

  • Alasdair Gibb

    (Physiology and Pharmacology, University College London)

  • Patricia C. Salinas

    (University College London)

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.

Suggested Citation

  • Lorenza Ciani & Aude Marzo & Kieran Boyle & Eleanna Stamatakou & Douglas M. Lopes & Derek Anane & Faye McLeod & Silvana B. Rosso & Alasdair Gibb & Patricia C. Salinas, 2015. "Wnt signalling tunes neurotransmitter release by directly targeting Synaptotagmin-1," Nature Communications, Nature, vol. 6(1), pages 1-13, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9302
    DOI: 10.1038/ncomms9302
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