Primary cilia are WNT-transducing organelles whose biogenesis is controlled by a WNT-PP1 axis

• DOI: 10.1016/j.devcel.2022.12.006
• Publication Date: 2023-01-23T15:43:08Z
• Authors: Kaiqing Zhang; Fabio Da Silva; Carina Seidl; Michaela Wilsch-B...; Jessica Herbst; Wieland B. Huttner; Christof Niehrs
• Keywords: Ciliogenesis; LRP6; LRP5; Beta-catenin; AXIN2

WNT signaling is important in development, stem cell maintenance, and disease. WNT ligands typically signal via receptor activation across the plasma membrane to induce β-catenin-dependent gene activation. Here, we show that in mammalian primary cilia, WNT receptors relay a WNT/GSK3 signal that β-catenin-independently promotes ciliogenesis. Characterization of a LRP6 ciliary targeting sequence and monitoring of acute WNT co-receptor activation (phospho-LRP6) support this conclusion. Ciliary WNT signaling inhibits protein phosphatase 1 (PP1) activity, a negative regulator of ciliogenesis, by preventing GSK3-mediated phosphorylation of the PP1 regulatory inhibitor subunit PPP1R2. Concordantly, deficiency of WNT/GSK3 signaling by depletion of cyclin Y and cyclin-Y-like protein 1 induces primary cilia defects in mouse embryonic neuronal precursors, kidney proximal tubules, and adult mice preadipocytes.