Encyclopedia of Signaling Molecules

Living Edition
| Editors: Sangdun Choi

FZD (Frizzled)

Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-6438-9_314-1


Historical Background

Drosophila frizzled (Dfz1) was originally identified as a causative gene for a mutant with disoriented cuticular hairs and was then cloned and characterized as a seven-transmembrane-type protein similar to G protein-coupled receptors (GPCRs) (Vinson and Adler 1987; Lagerström and Schiöth 2008). The phenotype of the Dfz1 mutant was the aberrant polarization of epithelial cells within the epithelial plane or the dysregulation of planar cell polarity (PCP). Drosophila mutants of dishevelled, Van Gogh (Vang or strabismus), prickle, diego, and starry night (flamingo) show phenotypes similar to the Dfz1 mutant. Dfz1, Dishevelled, Vang, Prickle, Diego and Starry night are characterized as core PCP components (Katoh 2005; Wu and Mlodzik 2009).



Synovial Sarcoma Williams Syndrome Planar Cell Polarity Neural Tube Defect Frizzle Receptor 
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  1. Bengoa-Vergniory N, Kypta RM. Canonical and noncanonical Wnt signaling in neural stem/progenitor cells. Cell Mol Life Sci. 2015;72:4157–72.CrossRefPubMedGoogle Scholar
  2. Bhanot P, Brink M, Samos CH, Hsieh JC, Wang Y, Macke JP, et al. A new member of the frizzled family from Drosophila functions as a Wingless receptor. Nature. 1996;382:225–30.CrossRefPubMedGoogle Scholar
  3. Botta A, Novelli G, Mari A, Novelli A, Sabani M, Korenberg J, et al. Detection of an atypical 7q11.23 deletion in Williams syndrome patients which does not include the STX1A and FZD9 genes. J Med Genet. 1999;36:478–80.PubMedPubMedCentralGoogle Scholar
  4. ClinicalTrials.gov database. US National Institute of Health. https://clinicaltrials.gov. Accessed 28 Aug 2016.
  5. Dawson K, Aflaki M, Nattel S. Role of the Wnt-Frizzled system in cardiac pathophysiology: a rapidly developing, poorly understood area with enormous potential. J Physiol. 2013;591:1409–32.CrossRefPubMedGoogle Scholar
  6. De Marco P, Merello E, Piatelli G, Cama A, Kibar Z, Capra V. Planar cell polarity gene mutations contribute to the etiology of human neural tube defects in our population. Birth Defects Res A Clin Mol Teratol. 2014;100:633–41.CrossRefPubMedGoogle Scholar
  7. Dijksterhuis JP, Petersen J, Schulte G. WNT/Frizzled signalling: receptor-ligand selectivity with focus on FZD-G protein signalling and its physiological relevance: IUPHAR Review 3. Br J Pharmacol. 2014;171:1195–209.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Katoh M. WNT/PCP signaling pathway and human cancer. Oncol Rep. 2005;14:1583–8.PubMedGoogle Scholar
  9. Katoh M, Katoh M. WNT signaling pathway and stem cell signaling network. Clin Cancer Res. 2007;13:4042–5.CrossRefPubMedGoogle Scholar
  10. Kirikoshi H, Sagara N, Koike J, Sekihara H, Hirai M, Katoh M. Molecular cloning and characterization of human Frizzled-4 on chromosome 11q14-q21. Biochem Biophys Res Commun. 1999;264:955–61.CrossRefPubMedGoogle Scholar
  11. Klaus A, Birchmeier W. Wnt signalling and its impact on development and cancer. Nat Rev Cancer. 2008;8:387–98.CrossRefPubMedGoogle Scholar
  12. Koike J, Takagi A, Miwa T, Hirai M, Terada M, Katoh M. Molecular cloning of Frizzled-10, a novel member of the Frizzled gene family. Biochem Biophys Res Commun. 1999;262:39–43.CrossRefPubMedGoogle Scholar
  13. Lagerström MC, Schiöth HB. Structural diversity of G protein-coupled receptors and significance for drug discovery. Nat Rev Drug Discov. 2008;7:339–57.CrossRefPubMedGoogle Scholar
  14. Liu C, Widen SA, Williamson KA, Ratnapriya R, Gerth-Kahlert C, Rainger J, et al. A secreted WNT-ligand-binding domain of FZD5 generated by a frameshift mutation causes autosomal dominant coloboma. Hum Mol Genet. 2016;25:1382–91.CrossRefPubMedGoogle Scholar
  15. Musada GR, Syed H, Jalali S, Chakrabarti S, Kaur I. Mutation spectrum of the FZD-4, TSPAN12 and ZNF408 genes in Indian FEVR patients. BMC Ophthalmol. 2016;16:90.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Nagayama S, Fukukawa C, Katagiri T, Okamoto T, Aoyama T, Oyaizu N, et al. Therapeutic potential of antibodies against FZD10, a cell-surface protein, for synovial sarcomas. Oncogene. 2005;24:6201–12.CrossRefPubMedGoogle Scholar
  17. Sagara N, Toda G, Hirai M, Terada M, Katoh M. Molecular cloning, differential expression, and chromosomal localization of human Frizzled-1, Frizzled-2, and Frizzled-7. Biochem Biophys Res Commun. 1998;252:117–22.CrossRefPubMedGoogle Scholar
  18. Simon EP, Freije CA, Farber BA, Lalazar G, Darcy DG, Honeyman JN, et al. Transcriptomic characterization of fibrolamellar hepatocellular carcinoma. Proc Natl Acad Sci U S A. 2015;112:E5916–25.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Swain RK, Katoh M, Medina A, Steinbeisser H. Xenopus frizzled-4 S, a splicing variant of Xfz4, is a context-dependent activator and inhibitor of Wnt/β-catenin signaling. Cell Commun Signal. 2005;3:12.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Vincan E, Barker N. The upstream components of the Wnt signalling pathway in the dynamic EMT and MET associated with colorectal cancer progression. Clin Exp Metastasis. 2008;25:657–63.CrossRefPubMedGoogle Scholar
  21. Vinson CR, Adler PN. Directional non-cell autonomy and the transmission of polarity information by the frizzled gene of Drosophila. Nature. 1987;329:549–51.CrossRefPubMedGoogle Scholar
  22. Wang Y, Chang H, Rattner A, Nathans J. Frizzled receptors in development and disease. Curr Top Dev Biol. 2016;117:113–39.CrossRefPubMedPubMedCentralGoogle Scholar
  23. Wen S, Zhu H, Lu W, Mitchell LE, Shaw GM, Lammer EJ, et al. Planar cell polarity pathway genes and risk for spina bifida. Am J Med Genet. 2010;152A:299–304.CrossRefPubMedPubMedCentralGoogle Scholar
  24. Wu J, Mlodzik M. A quest for the mechanism regulating global planar cell polarity of tissues. Trends Cell Biol. 2009;19:295–305.CrossRefPubMedPubMedCentralGoogle Scholar
  25. Zhang J, Carthew RW. Interactions between Wingless and Dfz2 during Drosophila wing development. Development. 1998;125:3075–85.PubMedGoogle Scholar

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© Springer Science+Business Media LLC 2016

Authors and Affiliations

  1. 1.Department of Omics NetworkNational Cancer CenterTokyoJapan