Table 1.
Summary of proteins associated with canonical/non-canonical Wnt signaling and cilia
| Canonical Wnt | Cilia or Wnt association | Reference |
|---|---|---|
| Wnt proteins | ||
| Inv (NPHP2) | Ciliary localization and physical interaction with Dvl | [65,66] |
| Dvl | Docking and polarization of basal bodies, basal body localization, targeted for degradation by Inv | [47,66] |
| Cilia-associated proteins | ||
| Bbs-associated | Hyperactive Wnt response in knockout cell lines | [68] |
| Kif3aa | Up regulation of cellular Wnt response in knockout cell lines and mutant mice | [68,69] |
| Ift88a | Up regulation of cellular Wnt response in mutant mice | [69,70] |
| Ift40 | Increase in expression of canonical Wnt pathway genes in kidney of mutant mice | [91] |
| Ift20 | Increase in nuclear beta-catenin and expression of Wnt target genes in kidney of mutant mice | [89] |
| Ofd1 | Up regulation of cellular Wnt response in mutant mice | [69] |
| Chibby | Binds beta-catenin preventing nuclear entry negatively regulating Wnt signaling | [71-73] |
| Seahorse | Binds to Dvl, constrains Wnt signaling in zebrafish | [74] |
| SREBP1c | Over expression disrupts ciliogenesis and increases canonical Wnt signaling in Xenopus. | [75] |
| Ahi1/Jbn | Abrogated Wnt signaling in kidney and cerebellum of mutant mice, facilitates beta-catenin entry into nucleus | [19,106,143] |
| Non-canonical Wnt | ||
| PCP effectors | ||
| Inturned | Highly expressed in ciliated tissue, required for ciliogenesis. Actin assembly, Rho localization, docking of basal bodies | [100,144,47,147] |
| Fuzzy | Required for axoneme elongation, predicted role in vesicular trafficking | [100,144] |
| Fritz | Expressed in ciliated tissue, required for ciliogenesis, mutations identified in human ciliopathies | [101] |
| Core PCP proteins | ||
| Dubroya | Regulates ciliogenesis, Apical Actin assembly | [148] |
| Frizzled | Defective ciliogenesis at zebrafish kupffers Vesicle | [148] |
| Dvl | Regulates ciliogenesis, Actin assembly, Rho localization, docking of basal bodies, associated with human ciliopathy proteins TMEM216 and TMEM67 | [47,149] |
| Celsr2/Celsr3 | Regulates ciliogenesis in multiciliated ependymal cells via basal body docking at apical plasma membrane | [150] |
| Prickle | Regulates cilium length in zebrafish | [151] |
| Vangl2a | Localizes to some cilia, xenopus basal body localization and ciliogenesis, zebrafish conflicting data | [82,83,96] |
aFurther described in the legend
The primary cilium was first implicated in suppression of canonical, β-catenin-dependent Wnt signaling, while being required for non-canonical Wnt signaling (PCP). One of the first studies to make this suggestion implicated inversin (Inv), a basal body protein associated with cystic kidney disease, as a molecular switch between the two Wnt signaling pathways. It was suggested that this occurred via targeting of cytoplasmic Dishevelled (Dvl) for degradation at the basal body. Another cilia-associated protein, the kinesin-like protein Kif3a, is thought to restrain canonical Wnt signaling by restricting the CK1-dependent phosphorylation of Dvl, which results in an active beta-catenin destruction complex, limiting beta-catenin induced transcription. It is possible that defects in protein interactions at the basal body, rather than in intraflagellar transport (IFT), could be responsible for dysregulation of Wnt signaling in cilia mutants. Such a suggestion is consistent with the findings that both IFT-mutant mice and mutant zebrafish do not show disruption of canonical Wnt signaling. aAxin 2 (Wnt target gene) and transgenic Wnt reporter normal in ift88, ift72, and kif3a mouse embryos [51]. No Wnt phenotype in ift88 zebrafish [52]. Conflicting zebrafish vangl2 data could be due to varying animal mutants and analysis methods.