Artículos de revistas
Wnt signalling tunes neurotransmitter release by directly targeting Synaptotagmin-1
Fecha
2015Registro en:
Ciani, Lorenza; Marzo, Aude; Boyle, Kieran; Stamatakou, Eleanna; Lopes, Douglas M.; et al.; Wnt signalling tunes neurotransmitter release by directly targeting Synaptotagmin-1; Macmillan Publishers; Nature Communications; 6; -1-2015; 1-13; 8302
2041-1723
Autor
Ciani, Lorenza
Marzo, Aude
Boyle, Kieran
Stamatakou, Eleanna
Lopes, Douglas M.
Anane, Derek
McLeod, Faye
Rosso, Silvana Beatriz
Gibb, Alasdair
Salinas, Patricia C.
Resumen
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.