| First Author | Zhang K | Year | 2023 |
| Journal | Dev Cell | Volume | 58 |
| Issue | 2 | Pages | 139-154.e8 |
| PubMed ID | 36693320 | Mgi Jnum | J:333039 |
| Mgi Id | MGI:7432262 | Doi | 10.1016/j.devcel.2022.12.006 |
| Citation | Zhang K, et al. (2023) Primary cilia are WNT-transducing organelles whose biogenesis is controlled by a WNT-PP1 axis. Dev Cell 58(2):139-154.e8 |
| abstractText | WNT signaling is important in development, stem cell maintenance, and disease. WNT ligands typically signal via receptor activation across the plasma membrane to induce beta-catenin-dependent gene activation. Here, we show that in mammalian primary cilia, WNT receptors relay a WNT/GSK3 signal that beta-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. |
