A novel conserved protein associates with the IFT-A complex to mediate nuclear translocation of β-catenin in Wg/Wnt-signaling

Summary Wingless (Wg)/Wnt signaling is critical throughout development and tissue homeostasis and associated with many disease states. Canonical Wg/Wnt-signaling is mediated by β-catenin (Arm in Drosophila ) with IFT-A/Kinesin-2 complex promoting nuclear translocation of β-catenin/Arm upon pathway activation. Although IFT-A is essential for nuclear translocation of β-catenin/Arm, existing data suggests additional proteins are involved in this process. Here, we have identified a novel, evolutionarily conserved protein, Pasovec (Psv), as a critical component required for nuclear β-catenin/Arm localization. We demonstrate that Psv functionally interacts with the IFT-A/Kinesin2 complex and physically associates with IFT140, a core component of IFT-A. The Psv-IFT140 interaction is independent of Wg/Wnt-signaling activation. Importantly, Psv contains a nuclear localization sequence (NLS), which is critical for its own nuclear localization and that of β-catenin/Arm upon Wg/Wnt-signaling activation. Psv with a mutated NLS can act as an inhibitor of Wg/Wnt-signaling. Altogether, this study describes a new factor required for Wg/Wnt-signaling, with its mutant phenotypes resembling wg and β-catenin/arm mutants, that functions during the nuclear translocation process of β-catenin/Arm. Full Text Availability The license terms selected by the author(s) for this preprint version do not permit archiving in PMC. The full text is available from the preprint server.