14-3-3ε and NAV2 interact to regulate neurite outgrowth and axon elongation

Neuron navigator 2 (NAV2) is required for all-trans retinoic acid (atRA) to induce neurite outgrowth in human neuroblastoma cells. Further, ectopic overexpression of full-length human NAV2 rescues an axonal elongation defect in the Caenorhabditis elegans unc-53 (NAV2 ortholog) mutant. Using a region of NAV2 that independently associates with the cytoskeleton as bait in a yeast-two-hybrid screen, 14-3-a epsilon was identified as a novel NAV2 interacting partner. Amino acids 761-960 of NAV2 are sufficient to confer a positive interaction with 14-3-3 epsilon as evidenced by a two-hybrid screen and co-immunoprecipitation assay. Knockdown of 14-3-3 epsilon leads to a decrease in atRA-mediated neurite outgrowth, similar to the elongation defects observed when NAV2 is depleted or mutated. Likewise, posterior lateral microtubule (PLM) defects in C elegans fed unc-53 RNAi are similar to those fed ftt-2 (14-3-3 homolog) RNAi. The discovery of an interaction between NAV2 and 14-3-3 epsilon could provide insight into the mechanism by which NAV2 participates in promoting cell migration and neuronal elongation. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.