Signaling across the synapse: a role for Wnt and Dishevelled in presynaptic assembly and neurotransmitter release.
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.
Ahmad-Annuar
Azlina
A
Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, England, UK.
Ciani
Lorenza
L
Simeonidis
Iordanis
I
Herreros
Judit
J
Fredj
Naila Ben
NB
Rosso
Silvana B
SB
Hall
Anita
A
Brickley
Stephen
S
Salinas
Patricia C
PC
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D000072261:Dishevelled Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010641:Phenotype; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017729:Presynaptic Terminals / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D051153:Wnt Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; C000606579:Dvl1 protein, mouse; D018377:Neurotransmitter Agents; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; C490508:Wnt7a protein, mouse