Wnt Signalling Promotes Actin Dynamics during Axon Remodelling through the Actin-Binding Protein XXXX .

@entity22222 @entity14840 @entity9762 @entity13020 @entity563 @entity26668 @entity1889 @entity9459
Upon arrival at their synaptic targets, axons slow down their growth and extensively remodel before the assembly of presynaptic boutons. Wnt proteins are target-derived secreted factors that promote axonal remodelling and synaptic assembly. In the developing spinal cord, Wnts secreted by motor neurons promote axonal remodelling of @entity14840 responsive dorsal root ganglia neurons. Axon remodelling induced by Wnts is characterised by growth cone pausing and enlargement, processes that depend on the re-organisation of microtubules. However, the contribution of the actin cytoskeleton has remained unexplored. Here, we demonstrate that @entity13020 regulates the actin cytoskeleton by rapidly inducing F-actin accumulation in growth cones from rodent DRG neurons through the scaffold protein @entity22222 ( @entity22222 ) and the @entity563 - @entity1889 kinase @entity9459 . Importantly, these changes in actin cytoskeleton occurs before enlargement of the growth cones is evident. Time-lapse imaging shows that @entity13020 @entity9762 and filopodia velocity. In addition, pharmacological inhibition of actin assembly demonstrates that @entity13020 increases actin dynamics. Through a yeast-two hybrid screen, we identified the actin-binding protein @entity26668 as a direct interactor of @entity22222 , a scaffold protein crucial for the Wnt signalling pathway. Gain of function of @entity26668 mimics Wnt-mediated axon remodelling, whereas @entity26668 silencing blocks the axon remodelling activity of @entity13020 . Importantly, blockade of the @entity22222 - @entity26668 interaction completely abolishes @entity13020 -mediated axonal remodelling. These findings demonstrate a novel role for Wnt- @entity22222 signalling through @entity26668 in the regulation of axonal remodeling.
