Mechanism of neurotransmitter release

Mechanism of neurotransmitter release

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, researchers investigated the interaction of release machinery proteins with Dishevelled-1 (Dvl1), a scaffold protein that determines the cellular locale of Wnt action.

Authors show in the journal Nature Communications 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.

These studies demonstrate that Wnt signalling tunes neurotransmitter release and identify Syt-1 as a target for modulation by secreted signalling proteins.