Figure 4.

Cilia-dependent Wnt signaling. The cilia/basal body may function as a regulatory switch to control the canonical and non-canonical Wnt signaling pathways. (A) In the absence of fluid flow, canonical Wnt signaling predominates. Wnt ligand binds to the co-receptors frizzled, dishevelled (DSH) is recruited to frizzled, and glycogen synthase kinase-3 (GSK3) is inactivated. β-catenin (β-cat) translocates to the nucleus, where it acts as a transcriptional co-activator with members of the LEF and TCF family and induces transcription of Wnt target genes such as cMYC, AXIN2, or L1CAM. (B) In non-canonical Wnt signaling, the mechanosensation by fluid flow causes intracellular Ca²⁺ increase and an increase inversin expression. Inversin resides in multiple locations in the cell as well as at the base of the cilium. Inversin targets cytoplasmic DSH for anaphase-promoting complex/cyclosome (APC/C)-dependent ubiquitylation and degradation, making it unavailable for canonical Wnt signaling.