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.[3]
↑Kirikoshi H, Sagara N, Koike J, Tanaka K, Sekihara H, Hirai M, Katoh M (Nov 1999). "Molecular cloning and characterization of human Frizzled-4 on chromosome 11q14-q21". Biochemical and Biophysical Research Communications. 264 (3): 955–61. doi:10.1006/bbrc.1999.1612. PMID10544037.
↑Xu Q, Wang Y, Dabdoub A, Smallwood PM, Williams J, Woods C, Kelley MW, Jiang L, Tasman W, Zhang K, Nathans J (March 2004). "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. doi:10.1016/S0092-8674(04)00216-8. PMID15035989.
Further reading
Li Y, Fuhrmann C, Schwinger E, Gal A, Laqua H (Jun 1992). "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. doi:10.1016/s0002-9394(14)74800-7. PMID1598965.
Sagara N, Kirikoshi H, Terasaki H, Yasuhiko Y, Toda G, Shiokawa K, Katoh M (Apr 2001). "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. doi:10.1006/bbrc.2001.4634. PMID11401527.
Takeda S, Kadowaki S, Haga T, Takaesu H, Mitaku S (Jun 2002). "Identification of G protein-coupled receptor genes from the human genome sequence". FEBS Letters. 520 (1–3): 97–101. doi:10.1016/S0014-5793(02)02775-8. PMID12044878.
Hering H, Sheng M (Jun 2002). "Direct interaction of Frizzled-1, -2, -4, and -7 with PDZ domains of PSD-95". FEBS Letters. 521 (1–3): 185–9. doi:10.1016/S0014-5793(02)02831-4. PMID12067714.
Chen W, ten Berge D, Brown J, Ahn S, Hu LA, Miller WE, Caron MG, Barak LS, Nusse R, Lefkowitz RJ (Sep 2003). "Dishevelled 2 recruits beta-arrestin 2 to mediate Wnt5A-stimulated endocytosis of Frizzled 4". Science. 301 (5638): 1391–4. doi:10.1126/science.1082808. PMID12958364.
Toomes C, Downey LM, Bottomley HM, Scott S, Woodruff G, Trembath RC, Inglehearn CF (Jan 2004). "Identification of a fourth locus (EVR4) for familial exudative vitreoretinopathy (FEVR)". Molecular Vision. 10: 37–42. PMID14737064.
Yao R, Natsume Y, Noda T (Aug 2004). "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. doi:10.1038/sj.onc.1207817. PMID15195140.
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 (Jul 2004). "Spectrum and frequency of FZD4 mutations in familial exudative vitreoretinopathy". Investigative Ophthalmology & Visual Science. 45 (7): 2083–90. doi:10.1167/iovs.03-1044. PMID15223780.
Omoto S, Hayashi T, Kitahara K, Takeuchi T, Ueoka Y (Jun 2004). "Autosomal dominant familial exudative vitreoretinopathy in two Japanese families with FZD4 mutations (H69Y and C181R)". Ophthalmic Genetics. 25 (2): 81–90. doi:10.1080/13816810490514270. PMID15370539.
Yoshida S, Arita R, Yoshida A, Tada H, Emori A, Noda Y, Nakao S, Fujisawa K, Ishibashi T (Oct 2004). "Novel mutation in FZD4 gene in a Japanese pedigree with familial exudative vitreoretinopathy". American Journal of Ophthalmology. 138 (4): 670–1. doi:10.1016/j.ajo.2004.05.001. PMID15488808.
Qin M, Hayashi H, Oshima K, Tahira T, Hayashi K, Kondo H (Aug 2005). "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. doi:10.1002/humu.20191. PMID15981244.
Nallathambi J, Shukla D, Rajendran A, Namperumalsamy P, Muthulakshmi R, Sundaresan P (2006). "Identification of novel FZD4 mutations in Indian patients with familial exudative vitreoretinopathy". Molecular Vision. 12: 1086–92. PMID17093393.