title: Wnt signalling tunes neurotransmitter release by directly targeting Synaptotagmin-1.
abstract: 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.
authors.affiliation: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Ciani
authors.affiliation: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
authors.forename: Aude
authors.initials: A
authors.lastname: Marzo
authors.affiliation: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
authors.forename: Kieran
authors.initials: K
authors.lastname: Boyle
authors.affiliation: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
authors.forename: Eleanna
authors.initials: E
authors.lastname: Stamatakou
authors.affiliation: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Lopes
authors.affiliation: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
authors.forename: Derek
authors.initials: D
authors.lastname: Anane
authors.affiliation: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
authors.forename: Faye
authors.initials: F
authors.lastname: McLeod
authors.affiliation: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
authors.forename: Silvana B
authors.initials: SB
authors.lastname: Rosso
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, UK.
authors.forename: Alasdair
authors.initials: A
authors.lastname: Gibb
authors.affiliation: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Salinas
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000072261:Dishevelled Proteins; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D047468:Immunoprecipitation; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009474:Neurons / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000378:metabolism*; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism*; D050863:Synaptotagmin I / Q000378:metabolism*; D050827:Syntaxin 1 / Q000378:metabolism*; D051153:Wnt Proteins / Q000235:genetics; D060449:Wnt Signaling Pathway
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; C000606579:Dvl1 protein, mouse; C000606580:Dvl1 protein, rat; D018377:Neurotransmitter Agents; D010750:Phosphoproteins; D050825:Synaptosomal-Associated Protein 25; D050863:Synaptotagmin I; D050827:Syntaxin 1; D051153:Wnt Proteins; C490508:Wnt7a protein, mouse