| Autor: |
Ciani L; Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK., Marzo A; Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK., Boyle K; Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK., Stamatakou E; Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK., Lopes DM; Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK., Anane D; Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK., McLeod F; Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK., Rosso SB; Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK., Gibb A; Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, UK., Salinas PC; Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK. |
| Abstrakt: |
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. |
