Wnt Signalling Promotes Actin Dynamics during Axon Remodelling through the Actin-Binding Protein Eps8

摘要: Upon arrival at their synaptic targets, axons slow down growth and extensively remodel before the assembly of presynaptic boutons. Wnt proteins are target-derived secreted factors that promote axonal remodelling assembly. In developing spinal cord, Wnts by motor neurons NT-3 responsive dorsal root ganglia neurons. Axon induced is characterised cone pausing enlargement, processes depend on re-organisation microtubules. However, contribution actin cytoskeleton has remained unexplored. Here, we demonstrate Wnt3a regulates rapidly inducing F-actin accumulation in cones from rodent DRG through scaffold protein Dishevelled-1 (Dvl1) serine-threonine kinase Gsk3β. Importantly, these changes occurs enlargement evident. Time-lapse imaging shows increases lamellar protrusion filopodia velocity. addition, pharmacological inhibition demonstrates dynamics. Through a yeast-two hybrid screen, identified actin-binding Eps8 as direct interactor Dvl1, crucial for signalling pathway. Gain function mimics Wnt-mediated axon remodelling, whereas silencing blocks activity Wnt3a. blockade Dvl1-Eps8 interaction completely abolishes Wnt3a-mediated remodelling. These findings novel role Wnt-Dvl1 regulation remodeling.