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Published 3 July 2006. doi:10.1083/jcb.200511054
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 174, Number 1, 127-139
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Article

Signaling across the synapse: a role for Wnt and Dishevelled in presynaptic assembly and neurotransmitter release



Azlina Ahmad-Annuar1, Lorenza Ciani1, Iordanis Simeonidis1, Judit Herreros1, Naila Ben Fredj1, Silvana B. Rosso1, Anita Hall1, Stephen Brickley2, and Patricia C. Salinas1

1 Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, England, UK
2 Department of Biological Sciences, Imperial College London, London SW8 2AY, England, UK

Correspondence to Patricia C. Salinas: p.salinas{at}ucl.ac.uk

Proper dialogue between presynaptic neurons and their targets is essential for correct synaptic assembly and function. At central synapses, Wnt proteins function as retrograde signals to regulate axon remodeling and the accumulation of presynaptic proteins. Loss of Wnt7a function leads to defects in the localization of presynaptic markers and in the morphology of the presynaptic axons. We show that loss of function of Dishevelled-1 (Dvl1) mimics and enhances the Wnt7a phenotype in the cerebellum. Although active zones appear normal, electrophysiological recordings in cerebellar slices from Wnt7a/Dvl1 double mutant mice reveal a defect in neurotransmitter release at mossy fiber–granule cell synapses. Deficiency in Dvl1 decreases, whereas exposure to Wnt increases, synaptic vesicle recycling in mossy fibers. Dvl increases the number of Bassoon clusters, and like other components of the Wnt pathway, it localizes to synaptic sites. These findings demonstrate that Wnts signal across the synapse on Dvl-expressing presynaptic terminals to regulate synaptic assembly and suggest a potential novel function for Wnts in neurotransmitter release.

A. Ahmad-Annuar, L. Ciani, I. Simeonidis, and J. Herreros contributed equally to this paper.

J. Herreros's present address is Hospital Universitari Arnau de Vilanova, Universitat de Lleida, 25198 Lleida, Spain.

A. Hall's present address is Dept. of Biological Sciences, Imperial College London, London SW8 2AY, UK.

Abbreviations used in this paper: ANOVA, analysis of variance; CASK, calmodulin-associated serine/threonine kinase; CM, conditioned media; DIV, days in vitro; FGF, fibroblast growth factor; GC, granule cell; mEPFC, miniature excitatory postsynaptic current; MF, mossy fiber; P, postnatal day.


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