frizzled receptors


Summary: A family of seven-pass transmembrane cell-surface proteins that combines with LOW DENSITY LIPROTEIN RECEPTOR-RELATED PROTEIN-5 or LOW DENSITY LIPROTEIN RECEPTOR-RELATED PROTEIN-5 to form receptors for WNT PROTEINS. Frizzled receptors often couple with HETEROTRIMERIC G PROTEINS and regulate the WNT SIGNALING PATHWAY.

Top Publications

  1. Drenser K, Dailey W, Vinekar A, Dalal K, Capone A, Trese M. Clinical presentation and genetic correlation of patients with mutations affecting the FZD4 gene. Arch Ophthalmol. 2009;127:1649-54 pubmed publisher
    ..Clinical Relevance Patients diagnosed with ROP may have a mutation in the FZD4 gene and display characteristics consistent with FEVR. Analysis of the FZD4 gene should be considered. ..
  2. Fukukawa C, Nagayama S, Tsunoda T, Toguchida J, Nakamura Y, Katagiri T. Activation of the non-canonical Dvl-Rac1-JNK pathway by Frizzled homologue 10 in human synovial sarcoma. Oncogene. 2009;28:1110-20 pubmed publisher
    ..Our results have strongly implied that FZD10 transactivation causes the activation of the non-canonical Dvl-Rac1-JNK pathway and plays critical roles in the development/progression of synovial sarcomas. ..
  3. MacDonald B, Tamai K, He X. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell. 2009;17:9-26 pubmed publisher
    ..Finally, we highlight some key aspects of Wnt/beta-catenin signaling in human diseases including congenital malformations, cancer, and osteoporosis, and discuss potential therapeutic implications. ..
  4. Nichols A, Floyd D, Bruinsma S, Narzinski K, Baranski T. Frizzled receptors signal through G proteins. Cell Signal. 2013;25:1468-75 pubmed publisher
    b>Frizzled receptors have long been thought to couple to G proteins but biochemical evidence supporting such an interaction has been lacking...
  5. Yu H, Ye X, Guo N, Nathans J. Frizzled 2 and frizzled 7 function redundantly in convergent extension and closure of the ventricular septum and palate: evidence for a network of interacting genes. Development. 2012;139:4383-94 pubmed publisher
  6. Maiti G, Naskar D, Sen M. The Wingless homolog Wnt5a stimulates phagocytosis but not bacterial killing. Proc Natl Acad Sci U S A. 2012;109:16600-5 pubmed publisher
  7. Yuzugullu H, Benhaj K, Ozturk N, Senturk S, Celik E, Toylu A, et al. Canonical Wnt signaling is antagonized by noncanonical Wnt5a in hepatocellular carcinoma cells. Mol Cancer. 2009;8:90 pubmed publisher
    ..TCF1 and TCF4 factors, and LRP5 and LRP6 co-receptors were ubiquitously expressed. Likewise, six Frizzled receptors, and canonical Wnt3 ligand were expressed in both subtypes...
  8. Carmon K, Lin Q, Gong X, Thomas A, Liu Q. LGR5 interacts and cointernalizes with Wnt receptors to modulate Wnt/?-catenin signaling. Mol Cell Biol. 2012;32:2054-64 pubmed publisher
    ..However, internalization of LGR5 does not appear to be essential for potentiating the canonical Wnt signaling pathway. ..
  9. Mukai A, Yamamoto Hino M, Awano W, Watanabe W, Komada M, Goto S. Balanced ubiquitylation and deubiquitylation of Frizzled regulate cellular responsiveness to Wg/Wnt. EMBO J. 2010;29:2114-25 pubmed publisher
    ..These results unveil a novel mechanism that regulates the cellular responsiveness to Wg/Wnt by controlling the cell surface level of Frizzled. ..

More Information


  1. Ueno K, Hazama S, Mitomori S, Nishioka M, Suehiro Y, Hirata H, et al. Down-regulation of frizzled-7 expression decreases survival, invasion and metastatic capabilities of colon cancer cells. Br J Cancer. 2009;101:1374-81 pubmed publisher
    ..001). These data suggest that FZD7 may be involved in enhancement of survival, invasion and metastatic capabilities of colon cancer cells through non-canonical Wnt signalling pathways as well as the canonical pathway. ..
  2. Sahores M, Gibb A, Salinas P. Frizzled-5, a receptor for the synaptic organizer Wnt7a, regulates activity-mediated synaptogenesis. Development. 2010;137:2215-25 pubmed publisher
    ..These findings support a model where neuronal activity and Wnts increase the responsiveness of neurons to Wnt signalling by recruiting Fz5 receptor at synaptic sites. ..
  3. Devenport D, Fuchs E. Planar polarization in embryonic epidermis orchestrates global asymmetric morphogenesis of hair follicles. Nat Cell Biol. 2008;10:1257-68 pubmed publisher
    ..Finally, we provide in vitro evidence that homotypic intracellular interactions of Celsr1 are required to recruit Vangl2 and Fzd6 to sites of cell-cell contact. ..
  4. Yu A, Xing Y, Harrison S, Kirchhausen T. Structural analysis of the interaction between Dishevelled2 and clathrin AP-2 adaptor, a critical step in noncanonical Wnt signaling. Structure. 2010;18:1311-20 pubmed publisher
    ..The crystal structure has thus allowed us to identify the specific interaction that leads to Frizzled uptake and to downstream, noncanonical signaling events. ..
  5. Nikopoulos K, Venselaar H, Collin R, Riveiro Alvarez R, Boonstra F, Hooymans J, et al. Overview of the mutation spectrum in familial exudative vitreoretinopathy and Norrie disease with identification of 21 novel variants in FZD4, LRP5, and NDP. Hum Mutat. 2010;31:656-66 pubmed publisher
    ..The increasing molecular understanding of Wnt signaling, related to ocular development and blood supply, offers more tools for accurate disease diagnosis that may be important in the development of therapeutic interventions. ..
  6. Mosca T, Schwarz T. The nuclear import of Frizzled2-C by Importins-beta11 and alpha2 promotes postsynaptic development. Nat Neurosci. 2010;13:935-43 pubmed publisher
    ..Thus, Wnt-activated growth of the postsynaptic membrane is mediated by the synapse-to-nucleus translocation and active nuclear import of Fz2-C via a selective Importin-beta11/alpha2 pathway. ..
  7. Sisson B, Topczewski J. Expression of five frizzleds during zebrafish craniofacial development. Gene Expr Patterns. 2009;9:520-7 pubmed publisher
    ..However, fzd7a is only expressed in the neural crest of the pharyngeal arches and fzd8a is expressed in the pharyngeal endoderm. ..
  8. Zhang K, Harada Y, Wei X, Shukla D, Rajendran A, Tawansy K, et al. An essential role of the cysteine-rich domain of FZD4 in Norrin/Wnt signaling and familial exudative vitreoretinopathy. J Biol Chem. 2011;286:10210-5 pubmed publisher
    ..This study identified a new class of FZD4 gene mutations in human disease and demonstrates a critical role of the CRD in Norrin binding and activation of the ?-catenin pathway. ..
  9. Pode Shakked N, Harari Steinberg O, Haberman Ziv Y, Rom Gross E, Bahar S, Omer D, et al. Resistance or sensitivity of Wilms' tumor to anti-FZD7 antibody highlights the Wnt pathway as a possible therapeutic target. Oncogene. 2011;30:1664-80 pubmed publisher
    ..FZD7 Ab therapy alone or in combination with Wnt pathway antagonists may have a significant role in the treatment of WT via targeting of a tumor progenitor population. ..
  10. Gray R, Roszko I, Solnica Krezel L. Planar cell polarity: coordinating morphogenetic cell behaviors with embryonic polarity. Dev Cell. 2011;21:120-33 pubmed publisher
    ..In vertebrates, by polarizing cilia in the node/Kupffer's vesicle, PCP signaling links the anteroposterior to left-right embryonic polarity. ..
  11. Strutt H, Strutt D. Differential stability of flamingo protein complexes underlies the establishment of planar polarity. Curr Biol. 2008;18:1555-64 pubmed publisher
  12. King T, Zhang W, Suto M, Li Y. Frizzled7 as an emerging target for cancer therapy. Cell Signal. 2012;24:846-51 pubmed publisher
    ..Therefore, targeted inhibition of Fzd7 represents a rational and promising new approach for cancer therapy. ..
  13. Struhl G, Casal J, Lawrence P. Dissecting the molecular bridges that mediate the function of Frizzled in planar cell polarity. Development. 2012;139:3665-74 pubmed publisher
    ..We propose that cells normally use this mechanism to read the local slope of tissue-wide gradients of Fz activity, so that all cells come to point in the same direction. ..
  14. Wu J, Mlodzik M. A quest for the mechanism regulating global planar cell polarity of tissues. Trends Cell Biol. 2009;19:295-305 pubmed publisher
    ..This review focuses on these exciting features and attempts to provide an integrated picture of these recent and novel insights. ..
  15. Miech C, Pauer H, He X, Schwarz T. Presynaptic local signaling by a canonical wingless pathway regulates development of the Drosophila neuromuscular junction. J Neurosci. 2008;28:10875-84 pubmed publisher
    ..This pathway thus provides a parallel mechanism to the postsynaptic activation of frizzled receptors and indicates that synaptic development results from the bidirectional influence of wingless on both ..
  16. Liu C, Nathans J. An essential role for frizzled 5 in mammalian ocular development. Development. 2008;135:3567-76 pubmed publisher
    ..These results demonstrate a central role for frizzled signaling in mammalian eye development and are likely to be relevant to the etiology of congenital human ocular anomalies. ..
  17. Sato A, Yamamoto H, Sakane H, Koyama H, Kikuchi A. Wnt5a regulates distinct signalling pathways by binding to Frizzled2. EMBO J. 2010;29:41-54 pubmed publisher
    ..These results suggest that Wnt5a regulates distinct pathways through receptor internalization-dependent and -independent mechanisms. ..
  18. van Amerongen R, Mikels A, Nusse R. Alternative wnt signaling is initiated by distinct receptors. Sci Signal. 2008;1:re9 pubmed publisher
    ..Here, we discuss basic principles of signal transduction initiated at the cell membrane, with the Wnt pathway, which harbors a multitude of ligands and receptors, as an example. ..
  19. Cordero J, Cagan R. Canonical wingless signaling regulates cone cell specification in the Drosophila retina. Dev Dyn. 2010;239:875-84 pubmed publisher
    ..This activity requires canonical Wg signaling and is linked with Notch pathway activity. Our work broadens the role of canonical Wg signaling to encompass multiple patterning steps in the emerging Drosophila retina. ..
  20. Robitaille J, Zheng B, Wallace K, Beis M, Tatlidil C, Yang J, et al. The role of Frizzled-4 mutations in familial exudative vitreoretinopathy and Coats disease. Br J Ophthalmol. 2011;95:574-9 pubmed publisher
    ..The authors identified 12 FEVR probands with FZD4 mutations. FZD4 mutation screening can be a useful tool especially in mild or atypical cases of FEVR. Germ-line mutations in FZD4 do not appear to be a common cause of Coats disease. ..
  21. Carmon K, Loose D. Development of a bioassay for detection of Wnt-binding affinities for individual frizzled receptors. Anal Biochem. 2010;401:288-94 pubmed publisher
    ..Wnt signaling is mediated by frizzled receptors (Fzds) at the cell surface and can be modulated by the secreted frizzled-related proteins (SFRPs) and other ..
  22. Matsumoto S, Fumoto K, Okamoto T, Kaibuchi K, Kikuchi A. Binding of APC and dishevelled mediates Wnt5a-regulated focal adhesion dynamics in migrating cells. EMBO J. 2010;29:1192-204 pubmed publisher
    ..These results suggest that the functional and physical interaction of Dvl and APC is involved in Wnt5a/Fz2-dependent focal adhesion dynamics during cell migration and epithelial morphogenesis. ..
  23. Laeremans H, Rensen S, Ottenheijm H, Smits J, Blankesteijn W. Wnt/frizzled signalling modulates the migration and differentiation of immortalized cardiac fibroblasts. Cardiovasc Res. 2010;87:514-23 pubmed publisher
    ..Therefore, Wnt/Fzd signalling may serve as a novel therapeutic target to ameliorate wound healing after MI. ..
  24. Vijayaragavan K, Szabo E, Bosse M, Ramos Mejia V, Moon R, Bhatia M. Noncanonical Wnt signaling orchestrates early developmental events toward hematopoietic cell fate from human embryonic stem cells. Cell Stem Cell. 2009;4:248-62 pubmed publisher
    ..Our study reveals an unappreciated role for noncanonical Wnt signaling in hESC specification that involves development of unique mesoderm precursors via morphogenic organization within human EBs. ..
  25. Konikoff C, Wisotzkey R, Newfeld S. Lysine conservation and context in TGFbeta and Wnt signaling suggest new targets and general themes for posttranslational modification. J Mol Evol. 2008;67:323-33 pubmed publisher
  26. Yan J, Huen D, Morely T, Johnson G, Gubb D, Roote J, et al. The multiple-wing-hairs gene encodes a novel GBD-FH3 domain-containing protein that functions both prior to and after wing hair initiation. Genetics. 2008;180:219-28 pubmed publisher
    ..This later function appears to be a feedback mechanism that limits cytoskeleton activation to ensure a single hair is formed. ..
  27. Vincan E, Flanagan D, Pouliot N, Brabletz T, Spaderna S. Variable FZD7 expression in colorectal cancers indicates regulation by the tumour microenvironment. Dev Dyn. 2010;239:311-7 pubmed publisher
    ..Thus, expression of FZD7 in colorectal cancer may be regulated by fibronectin in the microenvironment. ..
  28. Ye X, Wang Y, Cahill H, Yu M, Badea T, Smallwood P, et al. Norrin, frizzled-4, and Lrp5 signaling in endothelial cells controls a genetic program for retinal vascularization. Cell. 2009;139:285-98 pubmed publisher
  29. Boonstra F, van Nouhuys C, Schuil J, de Wijs I, van der Donk K, Nikopoulos K, et al. Clinical and molecular evaluation of probands and family members with familial exudative vitreoretinopathy. Invest Ophthalmol Vis Sci. 2009;50:4379-85 pubmed publisher
    ..To describe the ophthalmic characteristics and to identify the molecular cause of FEVR in a cohort of Dutch probands and their family members...
  30. Olguin P, Glavic A, Mlodzik M. Intertissue mechanical stress affects Frizzled-mediated planar cell polarity in the Drosophila notum epidermis. Curr Biol. 2011;21:236-42 pubmed publisher
  31. Wang Y, Chang H, Nathans J. When whorls collide: the development of hair patterns in frizzled 6 mutant mice. Development. 2010;137:4091-9 pubmed publisher
    ..Physical systems that undergo an analogous ordering of vector components suggest potential mechanisms that might apply to the patterning of hair follicles and related biological structures...
  32. Liu C, Bakeri H, Li T, Swaroop A. Regulation of retinal progenitor expansion by Frizzled receptors: implications for microphthalmia and retinal coloboma. Hum Mol Genet. 2012;21:1848-60 pubmed publisher
    ..Here, we have explored the role of two closely related Frizzled receptors, Fz5 and Fz8, in mouse retinal development...
  33. Pei J, Grishin N. Cysteine-rich domains related to Frizzled receptors and Hedgehog-interacting proteins. Protein Sci. 2012;21:1172-84 pubmed publisher
    ..Such a finding reinforces the evolutionary ties between the Wnt and Hedgehog signaling pathways and underscores the importance of gene duplications in creating essential signaling components in metazoan evolution. ..
  34. Díaz Prado S, Medina Villaamil V, Aparicio Gallego G, Blanco Calvo M, Lopez Cedrun J, Sironvalle Soliva S, et al. Expression of Wnt gene family and frizzled receptors in head and neck squamous cell carcinomas. Virchows Arch. 2009;455:67-75 pubmed publisher
    ..qPCR demonstrated that HNSCC express Wnt and Fz members, and suggested that Wnt and Fz signaling is activated in HNSCC cells. ..
  35. Grumolato L, Liu G, Mong P, Mudbhary R, Biswas R, Arroyave R, et al. Canonical and noncanonical Wnts use a common mechanism to activate completely unrelated coreceptors. Genes Dev. 2010;24:2517-30 pubmed publisher
    ..Thus, different Wnts, through their specific coupling and phosphorylation of unrelated coreceptors, activate completely distinct signaling pathways. ..
  36. Egger Adam D, Katanaev V. The trimeric G protein Go inflicts a double impact on axin in the Wnt/frizzled signaling pathway. Dev Dyn. 2010;239:168-83 pubmed publisher
    ..Thus, the two components of the trimeric Go protein mediate a double-direct and indirect-impact on different regions of Axin, which likely serves to ensure a robust inhibition of this protein and transduction of the Wnt signal. ..
  37. Jin X, Jeon H, Joo K, Kim J, Jin J, Kim S, et al. Frizzled 4 regulates stemness and invasiveness of migrating glioma cells established by serial intracranial transplantation. Cancer Res. 2011;71:3066-75 pubmed publisher
    ..Taken together, our results argue that Frizzled 4 is a member of the Wnt signaling family that governs both stemness and invasiveness of glioma stem cells, and that it may be a major cause of GBM recurrence and poor prognosis. ..
  38. Hogan J, Valentine M, Cox C, Doyle K, Collier S. Two frizzled planar cell polarity signals in the Drosophila wing are differentially organized by the Fat/Dachsous pathway. PLoS Genet. 2011;7:e1001305 pubmed publisher
    ..6) Altering the timing of ds knockdown during wing development can separate the role of the Ft/Ds pathway in wing morphogenesis from its role in Early Fz PCP signaling...
  39. van Amerongen R, Nusse R. Towards an integrated view of Wnt signaling in development. Development. 2009;136:3205-14 pubmed publisher
  40. Li L, Hutchins B, Kalil K. Wnt5a induces simultaneous cortical axon outgrowth and repulsive axon guidance through distinct signaling mechanisms. J Neurosci. 2009;29:5873-83 pubmed publisher
    ..We found that axon outgrowth is mediated by Ryk, whereas axon repulsion requires both Ryk and Frizzled receptors. Both receptors mediate Wnt-evoked fluctuations in intracellular calcium, which is required for increased ..
  41. Yu H, Smallwood P, Wang Y, Vidaltamayo R, Reed R, Nathans J. Frizzled 1 and frizzled 2 genes function in palate, ventricular septum and neural tube closure: general implications for tissue fusion processes. Development. 2010;137:3707-17 pubmed publisher
    ..These observations indicate that frizzled signaling is involved in diverse tissue closure processes, defects in which account for some of the most common congenital anomalies in humans...
  42. Cui X, Xing Y, Chen J, Dong S, Ying D, Yew D. Wnt/beta-catenin is involved in the proliferation of hippocampal neural stem cells induced by hypoxia. Ir J Med Sci. 2011;180:387-93 pubmed publisher
    ..NSCs proliferation was inhibited by transfecting with pAxin, whereas promoted by transfecting with p?-catenin. Hypoxia could enhance the proliferation of hippocampal NSCs and ?-catenin contributed to this action. ..
  43. Neumann J, Schaale K, Farhat K, Endermann T, Ulmer A, Ehlers S, et al. Frizzled1 is a marker of inflammatory macrophages, and its ligand Wnt3a is involved in reprogramming Mycobacterium tuberculosis-infected macrophages. FASEB J. 2010;24:4599-612 pubmed publisher
    ..The current data support the notion that evolutionarily conserved Wnt/Fzd signaling is involved in balancing the inflammatory response to microbial stimulation of innate immune cells of vertebrate origin. ..
  44. Fröjmark A, Schuster J, Sobol M, Entesarian M, Kilander M, Gabrikova D, et al. Mutations in Frizzled 6 cause isolated autosomal-recessive nail dysplasia. Am J Hum Genet. 2011;88:852-860 pubmed publisher
    ..Thus, our combined results show that FZD6 mutations can result in severe defects in nail and claw formation through reduced or abolished membranous FZD(6) levels and several nonfunctional WNT-FZD pathways...
  45. Warrington S, Strutt H, Strutt D. The Frizzled-dependent planar polarity pathway locally promotes E-cadherin turnover via recruitment of RhoGEF2. Development. 2013;140:1045-54 pubmed publisher
    ..We thus reveal a general mechanism by which the core planar polarity pathway can promote polarised cell rearrangements. ..
  46. Melchior K, Weiss J, Zaehres H, Kim Y, Lutzko C, Roosta N, et al. The WNT receptor FZD7 contributes to self-renewal signaling of human embryonic stem cells. Biol Chem. 2008;389:897-903 pubmed publisher
    ..These findings identify the WNT receptor FZD7 as a novel ES cell-specific surface antigen with a likely important role in the maintenance of ES cell self-renewal capacity. ..
  47. Sen M, Ghosh G. Transcriptional outcome of Wnt-Frizzled signal transduction in inflammation: evolving concepts. J Immunol. 2008;181:4441-5 pubmed
    ..We will discuss how Wnt-Frizzled signaling may initiate/augment inflammation, focusing on its transcriptional outcome. ..
  48. Rodriguez Gil D, Greer C. Wnt/Frizzled family members mediate olfactory sensory neuron axon extension. J Comp Neurol. 2008;511:301-17 pubmed publisher
    ..Our data point to a key role for Wnt/Fz molecules in the development of the mouse olfactory system, providing complementary mechanisms required for OSN axon extension and coalescence. ..
  49. Ohba S, Lanigan T, Roessler B. Leptin receptor JAK2/STAT3 signaling modulates expression of Frizzled receptors in articular chondrocytes. Osteoarthritis Cartilage. 2010;18:1620-9 pubmed publisher
  50. Armstrong A, Ryu Y, Chieco D, Kuruvilla R. Frizzled3 is required for neurogenesis and target innervation during sympathetic nervous system development. J Neurosci. 2011;31:2371-81 pubmed publisher
  51. Pan W, Choi S, Wang H, Qin Y, Volpicelli Daley L, Swan L, et al. Wnt3a-mediated formation of phosphatidylinositol 4,5-bisphosphate regulates LRP6 phosphorylation. Science. 2008;321:1350-3 pubmed publisher
    ..In turn, PtdIns (4,5)P2 regulated phosphorylation of LRP6 at Thr1479 and Ser1490. Therefore, our study reveals a signaling mechanism for Wnt to regulate LRP6 phosphorylation. ..
  52. Malbon C. Wnt signalling: the case of the 'missing' G-protein. Biochem J. 2011;433:e3-5 pubmed publisher
    ..Lensed from the fictional character of Sherlock Holmes, The Case of the Missing G-Protein is investigated. ..
  53. Bengochea A, de Souza M, Lefrancois L, Le Roux E, Galy O, Chemin I, et al. Common dysregulation of Wnt/Frizzled receptor elements in human hepatocellular carcinoma. Br J Cancer. 2008;99:143-50 pubmed publisher
    ..Expression patterns of all the 10 Frizzled receptors, and their extracellular soluble autoparacrine regulators (19 Wnt activators and 4 sFRP inhibitors) were ..