IQGAP1 Protein Regulates Nuclear Localization of β-Catenin via Importin-β5 Protein in Wnt Signaling

Background: The molecular mechanisms underlying the -catenin nuclear localization remain unclear. Results: IQGAP1 is a regulator of -catenin nuclear localization. Conclusion: Importin-5 and Ran contribute to the nuclear localization of -catenin. Significance: Novel molecular mechanisms were found in Wnt signaling. In the canonical Wnt signaling pathway, the translocation of -catenin is important for the activation of target genes in the nucleus. However, the molecular mechanisms underlying its nuclear localization remain unclear. In the present study, we found IQGAP1 to be a regulator of -catenin function via importin-5. In Xenopus embryos, depletion of IQGAP1 reduced Wnt-induced nuclear accumulation of -catenin and expression of Wnt target genes during early embryogenesis. Depletion of endogenous importin-5 associated with IQGAP1 also reduced expression of Wnt target genes and the nuclear localization of IQGAP1 and -catenin. Moreover, a small GTPase, Ran1, contributes to the nuclear translocation of -catenin and the activation of Wnt target genes. These results suggest that IQGAP1 functions as a regulator of translocation of -catenin in the canonical Wnt signaling pathway.