Frizzled-4 Explained

Frizzled-4 (Fz-4) is a protein that in humans is encoded by the FZD4 gene.^{[1] [2] [3]} Fz-4 has also been designated as CD344 (cluster of differentiation 344).

Function

This gene is a member of the frizzled gene family. Members of this family encode seven-transmembrane domain proteins that are receptors for the Wingless type MMTV integration site family of signaling proteins. Frizzled-4 is the only representative of frizzled family members that binds strongly an additional ligand Norrin that is functionally similar but structurally different from Wingless type proteins.^[4] FZD4 signaling induced by Norrin regulates vascular development of vertebrate retina and controls important blood vessels in the ear. Most frizzled receptors are coupled to the beta-catenin canonical signaling pathway. This protein may play a role as a positive regulator of the Wingless type MMTV integration site signaling pathway. A transcript variant retaining intronic sequence and encoding a shorter isoform has been described, however, its expression is not supported by other experimental evidence.

See also

• Frizzled

Further reading

• Li Y, Fuhrmann C, Schwinger E, Gal A, Laqua H . The gene for autosomal dominant familial exudative vitreoretinopathy (Criswick-Schepens) on the long arm of chromosome 11 . American Journal of Ophthalmology . 113 . 6 . 712–3 . Jun 1992 . 1598965 . 10.1016/s0002-9394(14)74800-7.
• Tanaka S, Akiyoshi T, Mori M, Wands JR, Sugimachi K . A novel frizzled gene identified in human esophageal carcinoma mediates APC/beta-catenin signals . Proceedings of the National Academy of Sciences of the United States of America . 95 . 17 . 10164–9 . Aug 1998 . 9707618 . 21479 . 10.1073/pnas.95.17.10164 . 1998PNAS...9510164T . free .
• Sagara N, Kirikoshi H, Terasaki H, Yasuhiko Y, Toda G, Shiokawa K, Katoh M . FZD4S, a splicing variant of frizzled-4, encodes a soluble-type positive regulator of the WNT signaling pathway . Biochemical and Biophysical Research Communications . 282 . 3 . 750–6 . Apr 2001 . 11401527 . 10.1006/bbrc.2001.4634 .
• Takeda S, Kadowaki S, Haga T, Takaesu H, Mitaku S . Identification of G protein-coupled receptor genes from the human genome sequence . FEBS Letters . 520 . 1–3 . 97–101 . Jun 2002 . 12044878 . 10.1016/S0014-5793(02)02775-8 . 7116392 . free .
• Hering H, Sheng M . Direct interaction of Frizzled-1, -2, -4, and -7 with PDZ domains of PSD-95 . FEBS Letters . 521 . 1–3 . 185–9 . Jun 2002 . 12067714 . 10.1016/S0014-5793(02)02831-4 . 39243103 . free .
• Robitaille J, MacDonald ML, Kaykas A, Sheldahl LC, Zeisler J, Dubé MP, Zhang LH, Singaraja RR, Guernsey DL, Zheng B, Siebert LF, Hoskin-Mott A, Trese MT, Pimstone SN, Shastry BS, Moon RT, Hayden MR, Goldberg YP, Samuels ME . Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative vitreoretinopathy . Nature Genetics . 32 . 2 . 326–30 . Oct 2002 . 12172548 . 10.1038/ng957 . 21389657 .
• Chen W, ten Berge D, Brown J, Ahn S, Hu LA, Miller WE, Caron MG, Barak LS, Nusse R, Lefkowitz RJ . Dishevelled 2 recruits beta-arrestin 2 to mediate Wnt5A-stimulated endocytosis of Frizzled 4 . Science . 301 . 5638 . 1391–4 . Sep 2003 . 12958364 . 10.1126/science.1082808 . 2003Sci...301.1391C . 34975427 .
• Toomes C, Downey LM, Bottomley HM, Scott S, Woodruff G, Trembath RC, Inglehearn CF . Identification of a fourth locus (EVR4) for familial exudative vitreoretinopathy (FEVR) . Molecular Vision . 10 . 37–42 . Jan 2004 . 14737064 .
• Yao R, Natsume Y, Noda T . MAGI-3 is involved in the regulation of the JNK signaling pathway as a scaffold protein for frizzled and Ltap . Oncogene . 23 . 36 . 6023–30 . Aug 2004 . 15195140 . 10.1038/sj.onc.1207817 . free .
• Toomes C, Bottomley HM, Scott S, Mackey DA, Craig JE, Appukuttan B, Stout JT, Flaxel CJ, Zhang K, Black GC, Fryer A, Downey LM, Inglehearn CF . Spectrum and frequency of FZD4 mutations in familial exudative vitreoretinopathy . Investigative Ophthalmology & Visual Science . 45 . 7 . 2083–90 . Jul 2004 . 15223780 . 10.1167/iovs.03-1044 . free .
• Omoto S, Hayashi T, Kitahara K, Takeuchi T, Ueoka Y . Autosomal dominant familial exudative vitreoretinopathy in two Japanese families with FZD4 mutations (H69Y and C181R) . Ophthalmic Genetics . 25 . 2 . 81–90 . Jun 2004 . 15370539 . 10.1080/13816810490514270 . 32817238 .
• Yoshida S, Arita R, Yoshida A, Tada H, Emori A, Noda Y, Nakao S, Fujisawa K, Ishibashi T . Novel mutation in FZD4 gene in a Japanese pedigree with familial exudative vitreoretinopathy . American Journal of Ophthalmology . 138 . 4 . 670–1 . Oct 2004 . 15488808 . 10.1016/j.ajo.2004.05.001 .
• Qin M, Hayashi H, Oshima K, Tahira T, Hayashi K, Kondo H . Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes . Human Mutation . 26 . 2 . 104–12 . Aug 2005 . 15981244 . 10.1002/humu.20191 . 20271372 . free .
• Nallathambi J, Shukla D, Rajendran A, Namperumalsamy P, Muthulakshmi R, Sundaresan P . Identification of novel FZD4 mutations in Indian patients with familial exudative vitreoretinopathy . Molecular Vision . 12 . 1086–92 . 2006 . 17093393 .
• Mary Pat Moyer . Planutis K, Planutiene M, Moyer MP, Nguyen AV, Pérez CA, Holcombe RF . Regulation of norrin receptor frizzled-4 by Wnt2 in colon-derived cells . BMC Cell Biology . 8 . 12 . 2007 . 17386109 . 1847812 . 10.1186/1471-2121-8-12 . free .

External links

• Web site: Frizzled Receptors: FZD₄ . IUPHAR Database of Receptors and Ion Channels . International Union of Basic and Clinical Pharmacology . 2008-12-04 . 2016-03-03 . https://web.archive.org/web/20160303203357/http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=3062 . dead . ]
• GeneReviews/NCBI/NIH/UW entry on Familial Exudative Vitreoretinopathy, Autosomal Dominant

Notes and References

1. Kirikoshi H, Sagara N, Koike J, Tanaka K, Sekihara H, Hirai M, Katoh M . Molecular cloning and characterization of human Frizzled-4 on chromosome 11q14-q21 . Biochemical and Biophysical Research Communications . 264 . 3 . 955–61 . Nov 1999 . 10544037 . 10.1006/bbrc.1999.1612 .
2. Toomes C, Bottomley HM, Jackson RM, Towns KV, Scott S, Mackey DA, Craig JE, Jiang L, Yang Z, Trembath R, Woodruff G, Gregory-Evans CY, Gregory-Evans K, Parker MJ, Black GC, Downey LM, Zhang K, Inglehearn CF . Mutations in LRP5 or FZD4 underlie the common familial exudative vitreoretinopathy locus on chromosome 11q . American Journal of Human Genetics . 74 . 4 . 721–30 . Apr 2004 . 15024691 . 1181948 . 10.1086/383202 .
3. Web site: Entrez Gene: FZD4 frizzled homolog 4 (Drosophila).
4. Xu Q, Wang Y, Dabdoub A, Smallwood PM, Williams J, Woods C, Kelley MW, Jiang L, Tasman W, Zhang K, Nathans J . Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair . Cell . 116 . 6 . 883–895 . March 2004 . 15035989 . 10.1016/S0092-8674(04)00216-8 . 18687651 . free .