Wnt Regulates Axon Behavior through Changes in Microtubule Growth Directionality: A New Role for Adenomatous Polyposis Coli

摘要: Axon guidance and target-derived signals control axonal behavior by regulating the cytoskeleton through poorly defined mechanisms. In particular, how these signaling molecules regulate growth directionality of microtubules is not well understood. Here we examine effect Wnts on cone remodeling, a process that precedes synapse formation. Time-lapse recordings reveal Wnt3a rapidly inhibits translocation while inducing enlargement. These changes in are associated with organization microtubules. imaging EB3-GFP (green fluorescent protein)-labeled microtubule plus-ends demonstrates regulates directionality, resulting looping, pausing, remodeling. Analyses Dishevelled-1 (Dvl1) mutant neurons demonstrate Dvl1 required for Wnt-mediated reorganization axon Wnt directly affects unexpectedly adenomatous polyposis coli (APC) loss from plus-ends. Consistently, short hairpin RNA knockdown APC mimics function. Together, our findings define as key target regulation direction.