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Gene Review

fz2  -  frizzled 2

Drosophila melanogaster

Synonyms: CG9739, D-Fz2, D-fz2, DFZ2, DFz-2, ...
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Disease relevance of fz2

  • Agents that inhibit specific G-protein subunits, pertussis toxin, GDP-beta-S and alpha-transducin also inhibit the calcium release triggered by Xwnt-5a and rat Frizzled-2 [1].

High impact information on fz2

  • While previous results indicate that loss of function for fz has tissue polarity defects, loss-of-function effects of Dfz2 are not known [2].
  • Wg signaling represses Dfz2 expression, creating a gradient of decreasing Wg stability moving toward the D/V boundary [3].
  • Genesis of epithelial planar polarity requires Frizzled, whereas Dfz2 affects morphogenesis by wingless-mediated signaling [4].
  • Recent studies at Drosophila glutamatergic synapses suggest that Wingless is secreted by motor neuron terminals and binds to postsynaptic Drosophila Frizzled-2 (DFz2) receptors [5].
  • Finally, we present strong evidence showing that an immunoprecipitated genomic DNA fragment corresponds to a promoter region involved in the direct regulation of frizzled2 expression by engrailed in vivo [6].

Biological context of fz2


Anatomical context of fz2

  • The fz-1 and fz-2 genes are widely expressed in rat tissues with the highest steady-state levels of mRNA in kidney, liver, heart, uterus, and ovary. fz-1 and -2 mRNA levels were greater in neonatal than in corresponding adult tissues [10].
  • Subsequently, Wg, Arrow and DFz2 are trafficked through the endocytic pathway to the lysosome, where they are degraded in a hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)-dependent manner [11].

Physical interactions of fz2

  • Wingless binds the seven-pass transmembrane DFrizzled2 receptor, but the ensuing events at synapses are not known [12].

Other interactions of fz2


Analytical, diagnostic and therapeutic context of fz2

  • Moreover, coimmunoprecipitation experiments in transfected cells and yeast two-hybrid assays suggest that the C terminus of DFz2 interacts directly with the PDZ domains 4 and 5 [5].


  1. Interaction of Wnt and a Frizzled homologue triggers G-protein-linked phosphatidylinositol signalling. Slusarski, D.C., Corces, V.G., Moon, R.T. Nature (1997) [Pubmed]
  2. frizzled and frizzled 2 play a partially redundant role in wingless signaling and have similar requirements to wingless in neurogenesis. Bhat, K.M. Cell (1998) [Pubmed]
  3. Wingless repression of Drosophila frizzled 2 expression shapes the Wingless morphogen gradient in the wing. Cadigan, K.M., Fish, M.P., Rulifson, E.J., Nusse, R. Cell (1998) [Pubmed]
  4. Dishevelled activates JNK and discriminates between JNK pathways in planar polarity and wingless signaling. Boutros, M., Paricio, N., Strutt, D.I., Mlodzik, M. Cell (1998) [Pubmed]
  5. Nuclear trafficking of Drosophila Frizzled-2 during synapse development requires the PDZ protein dGRIP. Ataman, B., Ashley, J., Gorczyca, D., Gorczyca, M., Mathew, D., Wichmann, C., Sigrist, S.J., Budnik, V. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  6. Genome-wide identification of in vivo Drosophila Engrailed-binding DNA fragments and related target genes. Solano, P.J., Mugat, B., Martin, D., Girard, F., Huibant, J.M., Ferraz, C., Jacq, B., Demaille, J., Maschat, F. Development (2003) [Pubmed]
  7. Non-equivalent roles of Drosophila Frizzled and Dfrizzled2 in embryonic wingless signal transduction. Moline, M.M., Dierick, H.A., Southern, C., Bejsovec, A. Curr. Biol. (2000) [Pubmed]
  8. Frizzled and Dfrizzled-2 function as redundant receptors for Wingless during Drosophila embryonic development. Bhanot, P., Fish, M., Jemison, J.A., Nusse, R., Nathans, J., Cadigan, K.M. Development (1999) [Pubmed]
  9. Overexpression of components of the Frizzled-Dishevelled cascade results in apoptotic cell death, mediated by beta-catenin. van Gijn, M.E., Snel, F., Cleutjens, J.P., Smits, J.F., Blankesteijn, W.M. Exp. Cell Res. (2001) [Pubmed]
  10. Two homologs of the Drosophila polarity gene frizzled (fz) are widely expressed in mammalian tissues. Chan, S.D., Karpf, D.B., Fowlkes, M.E., Hooks, M., Bradley, M.S., Vuong, V., Bambino, T., Liu, M.Y., Arnaud, C.D., Strewler, G.J. J. Biol. Chem. (1992) [Pubmed]
  11. Endocytic trafficking of Wingless and its receptors, Arrow and DFrizzled-2, in the Drosophila wing. Rives, A.F., Rochlin, K.M., Wehrli, M., Schwartz, S.L., Dinardo, S. Dev. Biol. (2006) [Pubmed]
  12. Wingless signaling at synapses is through cleavage and nuclear import of receptor DFrizzled2. Mathew, D., Ataman, B., Chen, J., Zhang, Y., Cumberledge, S., Budnik, V. Science (2005) [Pubmed]
  13. Wnt/Wingless signaling through beta-catenin requires the function of both LRP/Arrow and frizzled classes of receptors. Schweizer, L., Varmus, H. BMC Cell Biol. (2003) [Pubmed]
  14. Dally cooperates with Drosophila Frizzled 2 to transduce Wingless signalling. Lin, X., Perrimon, N. Nature (1999) [Pubmed]
  15. Dfrizzled-3, a new Drosophila Wnt receptor, acting as an attenuator of Wingless signaling in wingless hypomorphic mutants. Sato, A., Kojima, T., Ui-Tei, K., Miyata, Y., Saigo, K. Development (1999) [Pubmed]
  16. DWnt4 regulates cell movement and focal adhesion kinase during Drosophila ovarian morphogenesis. Cohen, E.D., Mariol, M.C., Wallace, R.M., Weyers, J., Kamberov, Y.G., Pradel, J., Wilder, E.L. Dev. Cell (2002) [Pubmed]
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