| First Author | Ciani L | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 8302 | PubMed ID | 26400647 |
| Mgi Jnum | J:227221 | Mgi Id | MGI:5699934 |
| Doi | 10.1038/ncomms9302 | Citation | Ciani L, et al. (2015) Wnt signalling tunes neurotransmitter release by directly targeting Synaptotagmin-1. Nat Commun 6:8302 |
| abstractText | 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. |
