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Kinesin-2 and IFT-A act as a complex promoting nuclear localization of β-catenin during Wnt signalling

Author

Listed:
  • Linh T. Vuong

    (Icahn School of Medicine at Mount Sinai)

  • Carlo Iomini

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Sophie Balmer

    (Icahn School of Medicine at Mount Sinai
    Sloan Kettering Institute)

  • Davide Esposito

    (Icahn School of Medicine at Mount Sinai)

  • Stuart A. Aaronson

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Marek Mlodzik

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

Abstract

Wnt/Wg-signalling is critical signalling in all metazoans. Recent studies suggest that IFT-A proteins and Kinesin-2 modulate canonical Wnt/Wg-signalling independently of their ciliary role. Whether they function together in Wnt-signalling and their mechanistic role in the pathway remained unresolved. Here we demonstrate that Kinesin-2 and IFT-A proteins act as a complex during Drosophila Wg-signalling, affecting pathway activity in the same manner, interacting genetically and physically, and co-localizing with β-catenin, the mediator of Wnt/Wg-signalling on microtubules. Following pathway activation, Kinesin-2/IFT-A mutant cells exhibit high cytoplasmic β-catenin levels, yet fail to activate Wg-targets. In mutant tissues in both, Drosophila and mouse/MEFs, nuclear localization of β-catenin is markedly reduced. We demonstrate a conserved, motor-domain dependent function of the Kinesin-2/IFT-A complex in promoting nuclear translocation of β-catenin. We show that this is mediated by protecting β-catenin from a conserved cytoplasmic retention process, thus identifying a mechanism for Kinesin-2/IFT-A in Wnt-signalling that is independent of their ciliary role.

Suggested Citation

  • Linh T. Vuong & Carlo Iomini & Sophie Balmer & Davide Esposito & Stuart A. Aaronson & Marek Mlodzik, 2018. "Kinesin-2 and IFT-A act as a complex promoting nuclear localization of β-catenin during Wnt signalling," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07605-z
    DOI: 10.1038/s41467-018-07605-z
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