title: 14-3-3ε and NAV2 interact to regulate neurite outgrowth and axon elongation.
abstract: 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, 14-3-3ε was identified as a novel NAV2 interacting partner. Amino acids 761-960 of NAV2 are sufficient to confer a positive interaction with 14-3-3ε as evidenced by a two-hybrid screen and co-immunoprecipitation assay. Knockdown of 14-3-3ε 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 14-3-3ε could provide insight into the mechanism by which NAV2 participates in promoting cell migration and neuronal elongation.
authors.affiliation: Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Marzinke
authors.forename: Terri
authors.initials: T
authors.lastname: Mavencamp
authors.forename: Joseph
authors.initials: J
authors.lastname: Duratinsky
authors.forename: Margaret
authors.initials: M
authors.lastname: Clagett-Dame
mesh_terms: D048948:14-3-3 Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D004265:DNA Helicases; D055785:Gene Knockdown Techniques; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D048948:14-3-3 Proteins; D029742:Caenorhabditis elegans Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; C465016:UNC-53 protein, C elegans; D014212:Tretinoin; D004265:DNA Helicases; C465311:NAV2 protein, human
keywords: 14-3-3ε; Axon elongation; NAV2; Neuron navigator 2; UNC-53; YWHAE