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bioRxiv · 10.1101/2025.06.21.660855

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

Vuong, L. T.·Mlodzik, M.
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Abstract

Wingless (Wg)/Wnt signaling is critical throughout development and tissue homeostasis and associated with many disease states. Canonical Wg/Wnt-signaling is mediated by {beta}-catenin (Arm in Drosophila) with IFT-A/Kinesin-2 complex promoting nuclear translocation of {beta}-catenin/Arm upon pathway activation. Although IFT-A is essential for nuclear translocation of {beta}-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 {beta}-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 {beta}-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 {beta}-catenin/arm mutants, that functions during the nuclear translocation process of {beta}-catenin/Arm.

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Vuong, L. T., Mlodzik, M.. 2025-06-23. A novel conserved protein associates with the IFT-A complex to mediate nuclear translocation of β-catenin in Wg/Wnt-signaling. https://doi.org/10.1101/2025.06.21.660855

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