Wnt5a evokes cortical axon outgrowth and repulsive guidance by tau mediated reorganization of dynamic microtubules.

摘要: Wnt5a guides cortical axons in vivo by repulsion and vitro evokes axon outgrowth calcium signaling pathways. Here we examined the role of microtubule (MT) reorganization dynamics mediating effects Wnt5a. Inhibiting MT with nocodazole taxol abolished evoked cultured hamster neurons. EGFP-EB3 labeled dynamic MTs visualized live cell imaging revealed that growth cone align nascent axon. increased from a splayed to bundled array oriented direction extension, gradients induced asymmetric redistribution toward far side cone. also transients were highest on Calcium could be linked tau, associated protein stabilizes MTs. Tau is phosphorylated at Ser 262 binding site CaMKII, required for repulsive turning. Phosphorylation tau Ser262 known detach increase their dynamics. Using transfection constructs mutated Ser262, found this guidance cones. Moreover, CaMKII inhibition prevents outgrowth, thus linking Wnt/calcium mediated during behaviors. © 2013 The Authors. Developmental Neurobiology Published Wiley Periodicals, Inc. Develop Neurobiol 74: 797–817, 2014