Table 1.
DVL-protein binding partners
| Binding partner | Pathway | Regulation | Function | References |
|---|---|---|---|---|
| DIX-domain binding proteins | ||||
| Axin | Canonical | Positive | β-catenin stability | [38] |
| Dishevelled | Canonical, non-canonical (PCP/Ca2+) | Positive | Enhances the ability of DVL activate Wnt pathway | [38] |
| Frodo | Canonical, Non-canonical | Positive | Secondary axis formation in Xenopus embryo | [57] |
| PDZ-domain binding proteins | ||||
| β-arrestin | Non-canonical (PCP) | Positive | Endocytosis of Frizzled receptor, β-catenin stability and activation of LEF transcription factor | [58–60] |
| Casein Kinase 1 | Canonical | Positive | Stimulate canonical pathway by phosphorylating DVL proteins | [61–63] |
| Casein Kinase 2 | Canonical | Positive | Stimulate canonical pathway by phosphorylating DVL proteins | [64] |
| CFTR | Canonical | Negative | Interacts with DVL-2, negatively regulates Wnt pathway | [81] |
| CXXC5 | Canonical | Negative | BMP4-induced inhibitor of Wnt Signaling in neural stem cell. Also plays a significant role in osteoblast differentiation and wound healing. | [36, 66–68] |
| DAAM1 | Non-canonical (PCP) | Positive | Rho A activation (Binds to both PDZ and DEP domain) | [26] |
| Dapper | Canonical, non-canonical (PCP) | Negative | Induces DVL degradation (Binds to both PDZ and DEP domain) | [82, 83] |
| Diego | Non-canonical (PCP) | Positive | Affects orientation of Drosophila wing hairs | [84] |
| FOXK1, FOXK2 (Forkhead box) | Canonical | Positive | Translocates DVL-2 to nucleus | [22] |
| Frizzled | Canonical, Non-canonical | Positive | Transduction of Wnt signal from Fz to downstream components, membrane targeting of Dishevelled | [43] |
| GSK3β-binding protein/Frat | Canonical, Non-canonical | Positive | Dissociation of Axin-GSK3β complex, activation of JNK | [85, 86] |
| IDAX/CXXC4 | Canonical | Negative | Regulate embryonic axis formation in Xenopus | [69] |
| Naked Cuticle | Non-canonical (PCP) | Negative | Repress Wnt pathway | [70, 71] |
| Notch | Non-canonical (PCP) | Negative | Regulate cell development in Drosophila eye, crosstalk between PCP and Notch pathway | [72–74] |
| PAR1 | Canonical, Non-canonical (PCP) | Positive / Negative | Phosphorylation of Dishevelled | [87–89] |
| Protein Phosphatase 2C | Canonical | Positive | Positively regulates Wnt signals by dephosphorylating Axin | [65] |
| RYK | Canonical | Positive | Essential for neurite outgrowth, activates T cell factor induced by Wnt ligands | [33] |
| Strabismus | Canonical, Non-canonical | Negative / Positive | Regulates planar cell polarity, morphogenetic movement and neural gene expression during gastrulation | [90, 91] |
| TMEM88 | Canonical | Negative | Disrupts canonical Wnt signaling | [92] |
| DEP-domain binding proteins | ||||
| APC | Non-canonical | Positive | Stabilization of microtubule, enhance cell migration | [93] |
| Diversion | Non-canonical | Positive | Regulates heart formation and gastrulation movements in zebrafish embryogenesis | [94] |
| Ephrin B1 | Non-canonical (PCP) | Positive | Regulates PCP pathway for cell movement and cell repulsion | [95–97] |
| Gpy | Canonical | Positive / Negative | Membrane localization of Dishevelled, and lysosomal degradation | [98, 99] |
| Prickle | Canonical, Non-canonical (PCP) | Negative | Degradation of DVL-3, regulate planar cell polarity | [84, 100, 101] |
| Protein Kinase C | Canonical/Non-canonical | Positive | Regulate convergent extension movements, phosphorylation and stabilization of DVL proteins | [102, 103] |
| Other associated proteins | ||||
| c-Jun | Canonical | Positive | Activates β-catenin/TCF mediated transcription of Wnt target genes in the nucleus | [16] |
| CTNNB1 | Canonical | Positive | Activate transcription of Wnt target genes | [16, 75] |
| KLHL12/Cullin-3 | Canonical | Negative | Degradation of Dishevelled 3 | [76] |
| IQGAP1 | Canonical | Positive | Promotes nuclear localization of Dishevelled which sequentially activates Wnt target genes | [104] |
| Lgl | Non-canonical | N/A | Regulate apical basal polarity | [77] |
| NFκB | NFκB signaling | Negative | DVL-1 (C-terminus) binds to p65 in nucleus and inhibits NFκB activation | [105] |
| RIPK4 | Canonical | Positive | Stimulates Wnt pathway by phosphorylating DVL proteins | [106] |
| RNF185 | Canonical | Negative | Negatively modulates osteoblast differentiation through ubiquitination and degradation of DVL-2 | [107] |
| SIRT1 | Canonical/Non-canonical | Positive | Positively regulates Wnt signaling via DVL proteins | [80] |
| TIAM1 (T-cell lymphoma invasion and metastasis 1) | Non-canonical | Positive | Mediates cell migration via Rac activation, required for neuron differentiation | [78, 79] |
*
Note: The table summarizes the list of proteins which bind to Dishevelled, categorized by the region of interaction with Dishevelled. The table further describes the pathway affected and the functional significance of the interaction between DVL and its associated proteins.