Genomes and Genes
Gene Symbol: fz2
Description: frizzled 2
Alias: CG9739, D-Fz2, D-fz2, DFZ2, DFz-2, DFz2, Dfrz2, Dfz2, Dfz[], Dm Fz2, Dmel\CG9739, FZ2, Fz2, dFz2, dfz(2), dfz2, dfz2r, frz2, fz-2, frizzled 2, CG9739-PA, CG9739-PB, CG9739-PC, CG9739-PD, CG9739-PE, CG9739-PF, CG9739-PG, D-frizzled2, DFrizzled2, Dfrizzled[], Frizzled2, drosophila frizzled 2, frizzled-2, fz2-PA, fz2-PB, fz2-PC, fz2-PD, fz2-PE, fz2-PF, fz2-PG
Species: fruit fly
- Yoshikawa S, McKinnon R, Kokel M, Thomas J. Wnt-mediated axon guidance via the Drosophila Derailed receptor. Nature. 2003;422:583-8 pubmed..Our results reveal an unexpected role in axon guidance for a Wnt family member, and show that the Derailed receptor is an essential component of Wnt signalling in these guidance events. ..
- Yanagawa S, Lee J, Ishimoto A. Identification and characterization of a novel line of Drosophila Schneider S2 cells that respond to wingless signaling. J Biol Chem. 1998;273:32353-9 pubmed..S2R+ cells are as sensitive to Wg as are clone 8 cells but can grow in simpler medium. Therefore, the S2R+ cell line is likely to prove highly useful for in vitro analyses of Wg signaling. ..
- Piddini E, Marshall F, Dubois L, Hirst E, Vincent J. Arrow (LRP6) and Frizzled2 cooperate to degrade Wingless in Drosophila imaginal discs. Development. 2005;132:5479-89 pubmed..We find that one of its signalling receptors, Frizzled2, stimulates Wingless internalization both in wing imaginal discs and cultured cells...
- Cadigan K, Fish M, Rulifson E, Nusse R. Wingless repression of Drosophila frizzled 2 expression shapes the Wingless morphogen gradient in the wing. Cell. 1998;93:767-77 pubmed..Here, we show that high levels of a Wg receptor, Drosophila frizzled 2 (Dfz2), stabilize Wg, allowing it to reach cells far from its site of synthesis...
- Korkut C, Ataman B, Ramachandran P, Ashley J, Barria R, Gherbesi N, et al. Trans-synaptic transmission of vesicular Wnt signals through Evi/Wntless. Cell. 2009;139:393-404 pubmed publisher..For a video summary of this article, see the PaperFlick file with the Supplemental Data available online. ..
- Tsai P, Wang M, Kao H, Cheng Y, Lin Y, Chen R, et al. Activity-dependent retrograde laminin A signaling regulates synapse growth at Drosophila neuromuscular junctions. Proc Natl Acad Sci U S A. 2012;109:17699-704 pubmed publisher..Our data indicate that synaptic activities down-regulate levels of the retrograde signal LanA to promote NMJ growth. ..
- Alexander C, Reichsman F, Hinkes M, Lincecum J, Becker K, Cumberledge S, et al. Syndecan-1 is required for Wnt-1-induced mammary tumorigenesis in mice. Nat Genet. 2000;25:329-32 pubmed..Our results provide both genetic and biochemical evidence that syndecan-1 can modulate Wnt signalling, and is critical for Wnt-1-induced tumorigenesis of the mouse mammary gland. ..
- Boutros M, Mihaly J, Bouwmeester T, Mlodzik M. Signaling specificity by Frizzled receptors in Drosophila. Science. 2000;288:1825-8 pubmed..Fz receptors can signal through beta-catenin-dependent and -independent pathways. In Drosophila, Fz and Fz2 are redundant receptors for Wg...
- Giraldez A, Cohen S. Wingless and Notch signaling provide cell survival cues and control cell proliferation during wing development. Development. 2003;130:6533-43 pubmed..However, only part of this effect was attributable to Notch-dependent induction of Wg, suggesting that other Notch-inducible signaling molecules contribute to the control of cell proliferation in the wing. ..
- He X, Semenov M, Tamai K, Zeng X. LDL receptor-related proteins 5 and 6 in Wnt/beta-catenin signaling: arrows point the way. Development. 2004;131:1663-77 pubmed..We also discuss the regulation of Lrp5/Lrp6 by other extracellular ligands, and LRP5 mutations associated with familial osteoporosis and other disorders. ..
- Moline M, Dierick H, Southern C, Bejsovec A. Non-equivalent roles of Drosophila Frizzled and Dfrizzled2 in embryonic wingless signal transduction. Curr Biol. 2000;10:1127-30 pubmed..patterning is performed by a single family member, Wingless (Wg), acting through its receptors Frizzled (Fz) and DFrizzled2 (Dfz2)...
- Hsieh J, Rattner A, Smallwood P, Nathans J. Biochemical characterization of Wnt-frizzled interactions using a soluble, biologically active vertebrate Wnt protein. Proc Natl Acad Sci U S A. 1999;96:3546-51 pubmed..Frizzled proteins, membrane anchored or secreted CRDs, and a set of insertion mutants in the CRD of Drosophila Frizzled 2. In a solid phase binding assay, the affinity of the XWnt8-alkaline phosphatase fusion for the purified ..
- Kennerdell J, Carthew R. Use of dsRNA-mediated genetic interference to demonstrate that frizzled and frizzled 2 act in the wingless pathway. Cell. 1998;95:1017-26 pubmed..Interference of the frizzled and Drosophila frizzled 2 genes together produced defects in embryonic patterning that mimic loss of wingless function...
- Katanaev V, Tomlinson A. Dual roles for the trimeric G protein Go in asymmetric cell division in Drosophila. Proc Natl Acad Sci U S A. 2006;103:6524-9 pubmed..Thus, Go likely integrates the signaling that directs the formation of the complex with the signaling that directs where the complex forms. ..
- Cong F, Schweizer L, Varmus H. Wnt signals across the plasma membrane to activate the beta-catenin pathway by forming oligomers containing its receptors, Frizzled and LRP. Development. 2004;131:5103-15 pubmed..In addition, the beta-catenin signaling mediated by ectopic expression of LRP is not dependent on Disheveled or Wnt, but can also be augmented by oligomerization of LRP receptors. ..
- Purvanov V, Koval A, Katanaev V. A direct and functional interaction between Go and Rab5 during G protein-coupled receptor signaling. Sci Signal. 2010;3:ra65 pubmed publisher..The interplay between heterotrimeric G proteins and Rab GTPases controlled receptor internalization, revealing a previously uncharacterized regulatory mechanism in GPCR signaling. ..
- Strapps W, Tomlinson A. Transducing properties of Drosophila Frizzled proteins. Development. 2001;128:4829-35 pubmedIn Drosophila, two closely related serpentine receptors, Frizzled (Fz) and D-Frizzled2 (Fz2) are able to act as receptors for the secreted Wnt peptide, Wingless (Wg)...
- Peradziryi H, Kaplan N, Podleschny M, Liu X, Wehner P, Borchers A, et al. PTK7/Otk interacts with Wnts and inhibits canonical Wnt signalling. EMBO J. 2011;30:3729-40 pubmed publisher..In Drosophila, Otk interacts with Wnt4 and opposes canonical Wnt signalling in embryonic patterning. We propose a model where PTK7/Otk functions in non-canonical Wnt signalling by turning off the canonical signalling branch. ..
- Wehrli M, Dougan S, Caldwell K, O KEEFE L, Schwartz S, Vaizel Ohayon D, et al. arrow encodes an LDL-receptor-related protein essential for Wingless signalling. Nature. 2000;407:527-30 pubmed..Thus, our data suggests a new and conserved function for this LRP subfamily in Wingless/Wnt signal reception. ..
- Rulifson E, Wu C, Nusse R. Pathway specificity by the bifunctional receptor frizzled is determined by affinity for wingless. Mol Cell. 2000;6:117-26 pubmed..found that the ligand-binding domain (CRD) of Fz has an approximately 10-fold lower affinity for Wg than the CRD of DFz2, a Wg receptor without polarity activity...
- Piddini E, Vincent J. Interpretation of the wingless gradient requires signaling-induced self-inhibition. Cell. 2009;136:296-307 pubmed publisher..Without lateral inhibition, some cells acquire ectopic fates. Lateral inhibition may be a general mechanism behind the interpretation of morphogen gradients. ..
- Shulman J, Perrimon N, Axelrod J. Frizzled signaling and the developmental control of cell polarity. Trends Genet. 1998;14:452-8 pubmed..Recently described examples from the nematode and frog suggest that the developmental control of cell polarity by FZ receptors might represent a functionally conserved signaling mechanism. ..
- Axelrod J, Miller J, Shulman J, Moon R, Perrimon N. Differential recruitment of Dishevelled provides signaling specificity in the planar cell polarity and Wingless signaling pathways. Genes Dev. 1998;12:2610-22 pubmed..Wingless (Wg) signaling also requires Dsh and may utilize DFz2 as a receptor...
- Hsieh J, Kodjabachian L, Rebbert M, Rattner A, Smallwood P, Samos C, et al. A new secreted protein that binds to Wnt proteins and inhibits their activities. Nature. 1999;398:431-6 pubmed
- Wu J, Jenny A, Mirkovic I, Mlodzik M. Frizzled-Dishevelled signaling specificity outcome can be modulated by Diego in Drosophila. Mech Dev. 2008;125:30-42 pubmed..Our data suggest that Dgo sequesters Dsh to a functionally distinct Fz/PCP signaling compartment within the cell. ..
- Sato A, Kojima T, Ui Tei K, Miyata Y, Saigo K. Dfrizzled-3, a new Drosophila Wnt receptor, acting as an attenuator of Wingless signaling in wingless hypomorphic mutants. Development. 1999;126:4421-30 pubmed..Wingless signaling may thus be attenuated by Dfrizzled-3 at least in wingless hypomorphic mutants. ..
- Bhat K. frizzled and frizzled 2 play a partially redundant role in wingless signaling and have similar requirements to wingless in neurogenesis. Cell. 1998;95:1027-36 pubmedThe Drosophila Frizzled (Fz) and Frizzled2 (DFz2) proteins function as receptors for Wingless (Wg) in tissue culture cells...
- Wu C, Nusse R. Ligand receptor interactions in the Wnt signaling pathway in Drosophila. J Biol Chem. 2002;277:41762-9 pubmed..We have therefore examined whether a soluble form of the Arrow molecule can bind to Wingless and Frizzled, but no interactions were detected. ..
- Zhang J, Carthew R. Interactions between Wingless and DFz2 during Drosophila wing development. Development. 1998;125:3075-85 pubmed..Wg protein has been shown in cell culture to functionally interact with DFz2, a receptor that is structurally related to the tissue polarity protein Frizzled (Fz)...
- Baeg G, Selva E, Goodman R, DasGupta R, Perrimon N. The Wingless morphogen gradient is established by the cooperative action of Frizzled and Heparan Sulfate Proteoglycan receptors. Dev Biol. 2004;276:89-100 pubmed..In addition, analyses of the two Fz proteins indicate that the Fz and DFz2 receptors, in addition to transducing the signal, modulate the slope of the Wg gradient by regulating the amount of ..
- Rives A, Rochlin K, Wehrli M, Schwartz S, Dinardo S. Endocytic trafficking of Wingless and its receptors, Arrow and DFrizzled-2, in the Drosophila wing. Dev Biol. 2006;293:268-83 pubmed..Here, we characterize the vesicular trafficking of Wg and its receptors, Arrow and DFrizzled-2 (DFz2), and investigate whether trafficking is important to regulate Wg signaling during dorsoventral patterning of the ..
- Wu J, Klein T, Mlodzik M. Subcellular localization of frizzled receptors, mediated by their cytoplasmic tails, regulates signaling pathway specificity. PLoS Biol. 2004;2:E158 pubmedThe Frizzled (Fz; called here Fz1) and Fz2 receptors have distinct signaling specificities activating either the canonical Wnt/beta-catenin pathway or Fz/planar cell polarity (PCP) signaling in Drosophila...
- Penton A, Wodarz A, Nusse R. A mutational analysis of dishevelled in Drosophila defines novel domains in the dishevelled protein as well as novel suppressing alleles of axin. Genetics. 2002;161:747-62 pubmed..We also recovered second-site-suppressing mutations in axin, mapping at a region that may specifically interact with overexpressed Dsh. ..
- Speese S, Ashley J, Jokhi V, Nunnari J, Barria R, Li Y, et al. Nuclear envelope budding enables large ribonucleoprotein particle export during synaptic Wnt signaling. Cell. 2012;149:832-46 pubmed publisher..We previously reported that during synapse development, a fragment of the Wnt-1 receptor, DFrizzled2, enters postsynaptic nuclei where it forms prominent foci...
- Tolwinski N, Wehrli M, Rives A, Erdeniz N, Dinardo S, Wieschaus E. Wg/Wnt signal can be transmitted through arrow/LRP5,6 and Axin independently of Zw3/Gsk3beta activity. Dev Cell. 2003;4:407-18 pubmed..We propose that Arrow (LRP) recruits Axin to the membrane, and that this interaction leads to Axin degradation. As a consequence, Armadillo is no longer bound by Axin, resulting in nuclear signaling by Armadillo. ..
- Packard M, Koo E, Gorczyca M, Sharpe J, Cumberledge S, Budnik V. The Drosophila Wnt, wingless, provides an essential signal for pre- and postsynaptic differentiation. Cell. 2002;111:319-30 pubmed..We suggest that Wg signals the coordinated development of pre- and postsynaptic compartments. ..
- Baeg G, Perrimon N. Functional binding of secreted molecules to heparan sulfate proteoglycans in Drosophila. Curr Opin Cell Biol. 2000;12:575-80 pubmed
- Ataman B, Ashley J, Gorczyca D, Gorczyca M, Mathew D, Wichmann C, et al. Nuclear trafficking of Drosophila Frizzled-2 during synapse development requires the PDZ protein dGRIP. Proc Natl Acad Sci U S A. 2006;103:7841-6 pubmed..suggest that Wingless is secreted by motor neuron terminals and binds to postsynaptic Drosophila Frizzled-2 (DFz2) receptors...
- Mathew D, Ataman B, Chen J, Zhang Y, Cumberledge S, Budnik V. Wingless signaling at synapses is through cleavage and nuclear import of receptor DFrizzled2. Science. 2005;310:1344-7 pubmed..Wingless binds the seven-pass transmembrane DFrizzled2 receptor, but the ensuing events at synapses are not known...
- Chen C, Struhl G. Wingless transduction by the Frizzled and Frizzled2 proteins of Drosophila. Development. 1999;126:5441-52 pubmed..Two members of the Frizzled (Fz) family of seven-pass transmembrane proteins, Drosophila Fz and Fz2, can bind Wg and are candidate Wg receptors...
- Dubois L, Lecourtois M, Alexandre C, Hirst E, Vincent J. Regulated endocytic routing modulates wingless signaling in Drosophila embryos. Cell. 2001;105:613-24 pubmed
- Kirkpatrick C, Dimitroff B, Rawson J, Selleck S. Spatial regulation of Wingless morphogen distribution and signaling by Dally-like protein. Dev Cell. 2004;7:513-23 pubmed..These findings suggest that modification of an HSPG by a secreted hydrolase can control morphogen levels in the matrix. ..
- Ataman B, Ashley J, Gorczyca M, Ramachandran P, Fouquet W, Sigrist S, et al. Rapid activity-dependent modifications in synaptic structure and function require bidirectional Wnt signaling. Neuron. 2008;57:705-18 pubmed publisher..Evoked activity induces Wnt1/Wg release from synaptic boutons, which stimulates both a postsynaptic DFz2 nuclear import pathway as well as a presynaptic pathway involving GSK-3beta/Shaggy...
- Bhanot P, Brink M, Samos C, Hsieh J, Wang Y, Macke J, et al. A new member of the frizzled family from Drosophila functions as a Wingless receptor. Nature. 1996;382:225-30 pubmed..show here that cultured Drosophila cells transfected with a novel member of the frizzled gene family in Drosophila, Dfz2, respond to added Wingless protein by elevating the level of the Armadillo protein...
- Strutt D. Frizzled signalling and cell polarisation in Drosophila and vertebrates. Development. 2003;130:4501-13 pubmed..This review discusses recent findings regarding non-canonical Frizzled signalling and cell polarisation. ..
- Moline M, Southern C, Bejsovec A. Directionality of wingless protein transport influences epidermal patterning in the Drosophila embryo. Development. 1999;126:4375-84 pubmed
- Marois E, Mahmoud A, Eaton S. The endocytic pathway and formation of the Wingless morphogen gradient. Development. 2006;133:307-17 pubmed..Thus, subcellular localization of Wingless along the apical-basal axis of receiving cells may be instrumental in shaping the Wingless gradient. ..
- Chen C, Strapps W, Tomlinson A, Struhl G. Evidence that the cysteine-rich domain of Drosophila Frizzled family receptors is dispensable for transducing Wingless. Proc Natl Acad Sci U S A. 2004;101:15961-6 pubmed..Thus, we infer that signal transduction does not require binding of Wg to the CRD, but instead depends on interactions between Wg and other portions of the receptor, or other proteins of the receptor complex. ..
- Strigini M, Cohen S. Wingless gradient formation in the Drosophila wing. Curr Biol. 2000;10:293-300 pubmed..Endocytosis is not required for Wg movement, but contributes to shaping the gradient by removing extracellular Wg. We propose that the extracellular Wg gradient forms by diffusion. ..
- Wong H, Bourdelas A, Krauss A, Lee H, Shao Y, Wu D, et al. Direct binding of the PDZ domain of Dishevelled to a conserved internal sequence in the C-terminal region of Frizzled. Mol Cell. 2003;12:1251-60 pubmed..Together, our results identify a missing molecular connection within the Wnt pathway. Differences in the binding affinity of the Dvl PDZ domain and its binding partners may be important in regulating signal transduction by Dvl. ..
- Srahna M, Leyssen M, Choi C, Fradkin L, Noordermeer J, Hassan B. A signaling network for patterning of neuronal connectivity in the Drosophila brain. PLoS Biol. 2006;4:e348 pubmed..JNK activity is necessary and sufficient for axon extension, whereas the antagonistic Wnt and FGF signals act to balance the extension and retraction required for the generation of the precise wiring pattern. ..
- Johnston L, Sanders A. Wingless promotes cell survival but constrains growth during Drosophila wing development. Nat Cell Biol. 2003;5:827-33 pubmed..We propose that the cell-survival- and growth-constraining activities of Wg function to sculpt and delimit final wing size as part of its overall patterning programme. ..
- Dani N, Nahm M, Lee S, Broadie K. A targeted glycan-related gene screen reveals heparan sulfate proteoglycan sulfation regulates WNT and BMP trans-synaptic signaling. PLoS Genet. 2012;8:e1003031 pubmed publisher..Anterograde Wg signaling via Wg receptor dFrizzled2 C-terminus nuclear import and retrograde Gbb signaling via synaptic MAD phosphorylation and nuclear import are ..
- 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..In Drosophila, the ligand Wingless causes the C terminus of its Frizzled2 receptor (Fz2-C) to be cleaved and translocated from the postsynaptic density to nuclei...
- Povelones M, Nusse R. The role of the cysteine-rich domain of Frizzled in Wingless-Armadillo signaling. EMBO J. 2005;24:3493-503 pubmed..We propose that Fz activates signaling in two steps: Fz uses its CRD to capture Wg, and once bound Wg interacts with the membrane portion of the receptor to initiate signaling. ..
- Djiane A, Yogev S, Mlodzik M. The apical determinants aPKC and dPatj regulate Frizzled-dependent planar cell polarity in the Drosophila eye. Cell. 2005;121:621-631 pubmed publisher..We propose a model whereby the dPatj/aPKC complex regulates PCP by inhibiting Fz1 in cells where it should not be active. ..
- Veeman M, Axelrod J, Moon R. A second canon. Functions and mechanisms of beta-catenin-independent Wnt signaling. Dev Cell. 2003;5:367-77 pubmed
- Lin X, Perrimon N. Dally cooperates with Drosophila Frizzled 2 to transduce Wingless signalling. Nature. 1999;400:281-4 pubmed..Our results indicate that Dally may act as a co-receptor for Wg, and that Dally, together with Drosophila Frizzled 2, modulates both short- and long-range activities of Wg.
- Yan D, Wu Y, Feng Y, Lin S, Lin X. The core protein of glypican Dally-like determines its biphasic activity in wingless morphogen signaling. Dev Cell. 2009;17:470-81 pubmed publisher..Based on these data, we propose that the principal function of Dlp is to retain Wg on the cell surface. As such, it can either compete with the receptor or provide ligands to the receptor, depending on the ratios of Wg, Fz2, and Dlp.
- Llimargas M, Lawrence P. Seven Wnt homologues in Drosophila: a case study of the developing tracheae. Proc Natl Acad Sci U S A. 2001;98:14487-92 pubmed..We suggest that the main advantage of retaining a number of similar genes is that it allows more subtle forms of control and more flexibility during evolution. ..
- Boutros M, Paricio N, Strutt D, Mlodzik M. Dishevelled activates JNK and discriminates between JNK pathways in planar polarity and wingless signaling. Cell. 1998;94:109-18 pubmed..Genesis of epithelial planar polarity requires Frizzled, whereas Dfz2 affects morphogenesis by wingless-mediated signaling. Dishevelled is required in both signaling pathways...
- Povelones M, Howes R, Fish M, Nusse R. Genetic evidence that Drosophila frizzled controls planar cell polarity and Armadillo signaling by a common mechanism. Genetics. 2005;171:1643-54 pubmed..This suggests that fz controls these two different signaling activities by a common mechanism. In addition, this screen yielded a set of missense mutations that identify amino acids specifically required for fz signaling function. ..
- Katanaev V, Ponzielli R, Semeriva M, Tomlinson A. Trimeric G protein-dependent frizzled signaling in Drosophila. Cell. 2005;120:111-22 pubmed..Thus, Go is likely part of a trimeric G protein complex that directly transduces Fz signals from the membrane to downstream components. ..
- Han C, Yan D, Belenkaya T, Lin X. Drosophila glypicans Dally and Dally-like shape the extracellular Wingless morphogen gradient in the wing disc. Development. 2005;132:667-79 pubmed..analyzed the roles of glypicans Dally and Dally-like protein (Dlp), the Wg receptors Frizzled (Fz) and Fz2, and the Wg co-receptor Arrow (Arr) in Wg gradient formation in the wing disc...
- Cohen E, Mariol M, Wallace R, Weyers J, Kamberov Y, Pradel J, et al. DWnt4 regulates cell movement and focal adhesion kinase during Drosophila ovarian morphogenesis. Dev Cell. 2002;2:437-48 pubmed..b>Dfrizzled2, Disheveled, and protein kinase C are also required...
- Mulligan K, Fuerer C, Ching W, Fish M, Willert K, Nusse R. Secreted Wingless-interacting molecule (Swim) promotes long-range signaling by maintaining Wingless solubility. Proc Natl Acad Sci U S A. 2012;109:370-7 pubmed publisher..In Drosophila, swim RNAi phenotypes resemble wg loss-of-function phenotypes in long-range signaling. We propose that Swim is a cofactor that promotes long-range Wg signaling in vivo by maintaining the solubility of Wg. ..
- Wu J, Mlodzik M. The frizzled extracellular domain is a ligand for Van Gogh/Stbm during nonautonomous planar cell polarity signaling. Dev Cell. 2008;15:462-9 pubmed publisher..Thus, direct Fz-Vang/Stbm interactions represent an intriguing mechanism that may account for the global orientation of cells within the plane of their epithelial field. ..
- Kleinschmit A, Koyama T, Dejima K, Hayashi Y, Kamimura K, Nakato H. Drosophila heparan sulfate 6-O endosulfatase regulates Wingless morphogen gradient formation. Dev Biol. 2010;345:204-14 pubmed publisher..Thus, Sulf1 participates in a feedback loop, potentially stabilizing the shape of the Wg gradient. Our study shows that the modification of HS fine structure provides a novel mechanism for the regulation of morphogen gradients. ..
- Bhanot P, Fish M, Jemison J, Nusse R, Nathans J, Cadigan K. Frizzled and Dfrizzled-2 function as redundant receptors for Wingless during Drosophila embryonic development. Development. 1999;126:4175-86 pubmedIn cell culture assays, Frizzled and Dfrizzled2, two members of the Frizzled family of integral membrane proteins, are able to bind Wingless and transduce the Wingless signal...