Wnt signalling tunes neurotransmitter release by directly targeting Synaptotagmin-1

CIANI, LORENZA; MARZO, AUDE; BOYLE, KIERAN; STAMATAKOU, ELEANNA; LOPES, DOUGLAS M.; ANANE, DEREK; MCLEOD, FAYE; ROSSO, SILVANA B.; GIBB, ALASDAIR; SALINAS, PATRICIA C.

NATURE COMMUNICATIONS

Nature Publishing Group

Año: 2015 vol. 6

2041-1723

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.