title: Neurite outgrowth involves adenomatous polyposis coli protein and beta-catenin.
abstract: Neuronal morphogenesis involves the initial formation of neurites and then differentiation of neurites into axons and dendrites. The mechanisms underlying neurite formation are poorly understood. A candidate protein for controlling neurite extension is the adenomatous polyposis coli (APC) protein, which regulates membrane extensions, microtubules and beta-catenin-mediated transcription downstream of Wnt signaling. APC is enriched at the tip of several neurites of unpolarized hippocampal neurons and the tip of only the long axon in polarized hippocampal neurons. Significantly, APC localized to the tip of only one neurite, marked by dephospho-tau as the future axon, before that neurite had grown considerably longer than other neurites. To determine whether neurite outgrowth was affected by beta-catenin accumulation and signaling, a stabilized beta-catenin mutant was expressed in PC12 cells, and neurite formation was measured. Stabilized beta-catenin mutants accumulated in APC clusters and inhibited neurite formation and growth. Importantly, these effects were also observed was independently of the gene transcriptional activity of beta-catenin. These results indicate that APC is involved in both early neurite outgrowth and increased growth of the future axon, and that beta-catenin has a structural role in inhibiting APC function in neurite growth.
authors.affiliation: Department of Biological Sciences, Stanford University, Beckman Center B121, Stanford, CA 94305, USA.
authors.forename: Violet
authors.initials: V
authors.lastname: Votin
authors.forename: W James
authors.initials: WJ
authors.lastname: Nelson
authors.forename: Angela I M
authors.initials: AI
authors.lastname: Barth
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism*; D000818:Animals; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism*; D009154:Mutation; D016501:Neurites / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D051176:beta Catenin