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Cilia Are Wnt Signaling Organelles
Wnt ligands typically signal via receptor activation across the plasma membrane to induce β-catenin-dependent gene activation. In contrast, we find that in primary- and motile cilia, Wnt receptors relay a Wnt /GSK3 signal that β-catenin-independently promotes ciliogenesis and ciliary beating. LRP6 contains a ciliary targeting sequence that locates the coreceptor to the ciliary membrane. Ciliary Wnt signalling inhibits protein phosphatase 1 (PP1) activity, a negative regulator of ciliogenesis, by decommissioning GSK3-mediated phosphorylation of the PP1 regulatory inhibitor subunit PPP1R2. Deficiency of Wnt /GSK3 signalling by depletion of cyclin Y and cyclin-Y-like protein 1 induces cilia defects in mouse and Xenopus embryos. We conclude that cilia are Wnt signalling organelles, which transduce a Wnt ┫PP1 signal that is distinct from that transmitted through the plasma membrane.
Speakers
Christof Niehrs