SpringerProtocols: Abstract: 10. β-Catenin-Independent Wnt Pathways: Signals, Core Proteins, and Effectors

10. β-Catenin-Independent Wnt Pathways: Signals, Core Proteins, and Effectors

By: Richard G. James³, William H. Conrad³, Randall T. Moon³

Abstract

Full Text

Download PDF (323K)

Wnt signaling activates several distinct intracellular pathways, which are important for cell proliferation, differentiation, and polarity. Wnt proteins are secreted molecules that typically signal across the membrane via interaction with the transmembrane receptor Frizzled. Following interaction with Frizzled, the downstream effect of the most widely studied Wnt pathway is stabilization and nuclear translocation of the cytosolic protein, β-catenin. In this chapter, we discuss two β-catenin-independent branches of Wnt signaling: 1) Wnt/planar cell polarity (PCP), a Wnt pathway that signals through the small GTPases, Rho and Rac, to promote changes in the actin cytoskeleton, and 2) Wnt/Ca²+, a Wnt pathway that promotes intracellular calcium transients and negatively regulates the Wnt/β-catenin pathway. Finally, during the course of our discussion, we highlight areas that require future research.

Affiliation(s): (3) Howard Hughes Medical Institute, Department of Pharmacology, and Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA, USA

Book Title: Wnt Signaling: Pathway Methods and Mammalian Models

Series: Methods in Molecular Biology | Volume: 468 | Pub. Date: Jul-01-2008 | Page Range: 131-144 | DOI: 10.1007/978-1-59745-249-6_10

Subject: Protein Science

Key Words: Wnt - Wnt/Ca - Wnt/PCP

References

Download References

1.	Moon, R.T., A.D. Kohn, G.V. De Ferrari, and A. Kaykas. (2004) WNT and beta-catenin signalling: diseases and therapies. Nat Rev Genet. 5, 691–701.

2.	Seifert, J.R. and M. Mlodzik. (2007) Friz-zled/PCP signalling: a conserved mechanism regulating cell polarity and directed motility. Nat Rev Genet. 8, 126–138.

3.	Wu, J., T.J. Klein, and M. Mlodzik. (2004) Subcellular localization of frizzled receptors, mediated by their cytoplasmic tails, regulates signaling pathway specificity. PLoS Biol. 2, E158.

4.	Amonlirdviman, K., N.A. Khare, D.R. Tree, W.S. Chen, J.D. Axelrod, and C.J. Tomlin. (2005) Mathematical modeling of planar cell polarity to understand domineering nonautonomy. Science. 307, 423–426.

5.	Yang, C.H., J.D. Axelrod, and M.A. Simon. (2002) Regulation of Frizzled by fat-like cadherins during planar polarity signaling in the Drosophila compound eye. Cell. 108, 675–688.

6.	Axelrod, J.D. (2001) Unipolar membrane association of Dishevelled mediates Frizzled planar cell polarity signaling. Genes Dev. 15, 1182–1187.

7.	Das, G., A. Jenny, T.J. Klein, S. Eaton, and M. Mlodzik. (2004) Diego interacts with Prickle and Strabismus/Van Gogh to localize planar cell polarity complexes. Development. 131, 4467–4476.

8.	Strutt, D.I. (2001) Asymmetric localization of frizzled and the establishment of cell polarity in the Drosophila wing. Mol Cell. 7, 367–375.

9.	Bastock, R., H. Strutt, and D. Strutt. (2003) Strabismus is asymmetrically localised and binds to Prickle and Dishevelled during Drosophila planar polarity patterning. Development. 130, 3007–3014.

10.	Tree, D.R., J.M. Shulman, R. Rousset, M.P. Scott, D. Gubb, and J.D. Axelrod. (2002) Prickle mediates feedback amplification to generate asymmetric planar cell polarity signaling. Cell. 109, 371–381.

11.	Jenny, A., J. Reynolds-Kenneally, G. Das, M. Burnett, and M. Mlodzik. (2005) Diego and Prickle regulate Frizzled planar cell polarity signalling by competing for Dishevelled binding. Nat Cell Biol. 7, 691–697.

12.	Usui, T., Y. Shima, Y. Shimada, S. Hirano, R.W. Burgess, T.L. Schwarz, et al. (1999) Flamingo, a seven-pass transmembrane cad-herin, regulates planar cell polarity under the control of Frizzled. Cell. 98, 585–595.

13.	Adler, P.N., J. Charlton, K.H. Jones, and J. Liu. (1994) The cold-sensitive period for frizzled in the development of wing hair polarity ends prior to the start of hair morphogenesis. Mech Dev. 46, 101–107.

14.	Eaton, S., R. Wepf, and K. Simons. (1996) Roles for Rac1 and Cdc42 in planar polarization and hair outgrowth in the wing of Drosophila. J Cell Biol. 135, 1277–1289.

15.	Fanto, M., U. Weber, D.I. Strutt, and M. Mlodzik. (2000) Nuclear signaling by Rac and Rho GTPases is required in the establishment of epithelial planar polarity in the Drosophila eye. Curr Biol. 10, 979–988.

16.	Schwarz-Romond, T., C. Asbrand, J. Bakkers, M. Kuhl, H.J. Schaeffer, J. Huelsken, et al. (2002) The ankyrin repeat protein Diversin recruits Casein kinase Iepsilon to the beta-catenin degradation complex and acts in both canonical Wnt and Wnt/JNK signaling. Genes Dev. 16, 2073–2084.

17.	Park, M. and R.T. Moon. (2002) The planar cell-polarity gene stbm regulates cell behaviour and cell fate in vertebrate embryos. Nat Cell Biol. 4, 20–25.

18.	Wallingford, J.B., B.A. Rowning, K.M. Vogeli, U. Rothbacher, S.E. Fraser, and R.M. Harland. (2000) Dishevelled controls cell polarity during Xenopus gastrulation. Nature. 405, 81–85.

19.	Wang, J., N.S. Hamblet, S. Mark, M.E. Dickinson, B.C. Brinkman, N. Segil, et al. (2006) Dishevelled genes mediate a conserved mammalian PCP pathway to regulate convergent extension during neurulation. Development. 133, 1767–1778.

20.	Formstone, C.J. and I. Mason. (2005) Combinatorial activity of Flamingo proteins directs convergence and extension within the early zebrafish embryo via the planar cell polarity pathway. Dev Biol. 282, 320–335.

21.	Takeuchi, M., J. Nakabayashi, T. Sakaguchi, T.S. Yamamoto, H. Takahashi, H. Takeda, et al. (2003) The prickle-related gene in vertebrates is essential for gastrulation cell movements. Curr Biol. 13, 674–679.

22.	Veeman, M.T., D.C. Slusarski, A. Kaykas, S.H. Louie, and R.T. Moon. (2003) Zebrafish prickle, a modulator of noncanonical Wnt/Fz signaling, regulates gastrulation movements. Curr Biol. 13, 680–685.

23.	Kilian, B., H. Mansukoski, F.C. Barbosa, F. Ulrich, M. Tada, and C.P. Heisenberg. (2003) The role of Ppt/Wnt5 in regulating cell shape and movement during zebrafish gastrulation. Mech Dev. 120, 467–476.

24.	Heisenberg, C.P., M. Tada, G.J. Rauch, L. Saude, M.L. Concha, R. Geisler, et al. (2000) Silberblick/Wnt11 mediates convergent extension movements during zebrafish gastrulation. Nature. 405, 76–81.

25.	Carreira-Barbosa, F., M.L. Concha, M. Takeuchi, N. Ueno, S.W. Wilson, and M. Tada. (2003) Prickle 1 regulates cell movements during gastrulation and neuronal migration in zebrafish. Development. 130, 4037–4046.

26.	Moeller, H., A. Jenny, H.J. Schaeffer, T. Schwarz-Romond, M. Mlodzik, M. Ham-merschmidt, et al. (2006) Diversin regulates heart formation and gastrulation movements in development. Proc Natl Acad Sci U S A. 103, 15900–15905.

27.	Axelrod, J.D., J.R. Miller, J.M. Shulman, R.T. Moon, and N. Perrimon. (1998) Differential recruitment of Dishevelled provides signaling specificity in the planar cell polarity and Wingless signaling pathways. Genes Dev. 12, 2610–2622.

28.	Boutros, M., J. Mihaly, T. Bouwmeester, and M. Mlodzik. (2000) Signaling specificity by Frizzled receptors in Drosophila. Science. 288, 1825–1828.

29.	Yanagawa, S., F. van Leeuwen, A. Wodarz, J. Klingensmith, and R. Nusse. (1995) The dishevelled protein is modified by wingless signaling in Drosophila. Genes Dev. 9, 1087–1097.

30.	Gonzalez-Sancho, J.M., K.R. Brennan, L.A. Castelo-Soccio, and A.M. Brown. (2004) Wnt proteins induce dishevelled phosphor-ylation via an LRP5/6- independent mechanism, irrespective of their ability to stabilize beta-catenin. Mol Cell Biol. 24, 4757–4768.

31.	Liu, T., A.J. DeCostanzo, X. Liu, H. Wang, S. Hallagan, R.T. Moon, et al. (2001) G protein signaling from activated rat frizzled-1 to the beta-catenin-Lef-Tcf pathway. Science. 292, 1718–1722.

32.	Cong, F., L. Schweizer, and H. Varmus. (2004) Casein kinase Iepsilon modulates the signaling specificities of dishevelled. Mol Cell Biol. 24, 2000–2011.

33.	Peters, J.M., R.M. McKay, J.P. McKay, and J.M. Graff. (1999) Casein kinase I transduces Wnt signals. Nature. 401, 345–350.

34.	Swiatek, W., I.C. Tsai, L. Klimowski, A. Pepler, J. Barnette, H.J. Yost, et al. (2004) Regulation of casein kinase I epsilon activity by Wnt signaling. J Biol Chem. 279, 13011–13017.

35.	Klein, T.J., A. Jenny, A. Djiane, and M. Mlodzik. (2006) CKIepsilon/discs overgrown promotes both Wnt-Fz/beta-catenin and Fz/PCP signaling in Drosophila. Curr Biol. 16, 1337–1343.

36.	Strutt, H., M.A. Price, and D. Strutt. (2006) Planar polarity is positively regulated by casein kinase Iepsilon in Drosophila. Curr Biol. 16, 1329–1336.

37.	Tao, Q., C. Yokota, H. Puck, M. Kofron, B. Birsoy, D. Yan, et al. (2005) Maternal wnt11 activates the canonical wnt signaling pathway required for axis formation in Xenopus embryos. Cell. 120, 857–871.

38.	Lu, W., V. Yamamoto, B. Ortega, and D. Baltimore. (2004) Mammalian Ryk is a Wnt coreceptor required for stimulation of neu-rite outgrowth. Cell. 119, 97–108.

39.	Hikasa, H., M. Shibata, I. Hiratani, and M. Taira. (2002) The Xenopus receptor tyrosine kinase Xror2 modulates morpho-genetic movements of the axial mesoderm and neuroectoderm via Wnt signaling. Development. 129, 5227–5239.

40.	Mikels, A.J. and R. Nusse. (2006) Purified Wnt5a protein activates or inhibits beta-cat-enin-TCF signaling depending on receptor context. PLoS Biol. 4, e115.

41.	Schambony, A. and D. Wedlich. (2007) Wnt-5A/Ror2 regulate expression of XPAPC through an alternative noncanonical signaling pathway. Dev Cell. 12, 779–792.

42.	Keeble, T.R., M.M. Halford, C. Seaman, N. Kee, M. Macheda, R.B. Anderson, et al. (2006) The Wnt receptor Ryk is required for Wnt5a-mediated axon guidance on the contralateral side of the corpus callosum. J Neurosci. 26, 5840–5848.

43.	Yoshikawa, S., R.D. McKinnon, M. Kokel, and J.B. Thomas. (2003) Wnt-mediated axon guidance via the Drosophila Derailed receptor. Nature. 422, 583–588.

44.	Lu, X., A.G. Borchers, C. Jolicoeur, H. Ray-burn, J.C. Baker, and M. Tessier-Lavigne. (2004) PTK7/CCK-4 is a novel regulator of planar cell polarity in vertebrates. Nature. 430, 93–98.

45.	He, X., J.P. Saint-Jeannet, Y. Wang, J. Nathans, I. Dawid, and H. Varmus. (1997) A member of the Frizzled protein family mediating axis induction by Wnt-5A. Science. 275, 1652–1654.

46.	Habas, R., Y. Kato, and X. He. (2001) Wnt/Frizzled activation of Rho regulates vertebrate gastrulation and requires a novel Formin homology protein Daam1. Cell. 107, 843–854.

47.	Price, M.H., D.M. Roberts, B.M. McCartney, E. Jezuit, and M. Peifer. (2006) Cytoskeletal dynamics and cell signaling during planar polarity establishment in the Drosophila embryonic denticle. J Cell Sci. 119, 403–415.

48.	Harris, K.E. and S.K. Beckendorf. (2007) Different Wnt signals act through the Frizzled and RYK receptors during Drosophila salivary gland migration. Development. 134, 2017–2025.

49.	Wong, L.L. and P.N. Adler. (1993) Tissue polarity genes of Drosophila regulate the subcellular location for prehair initiation in pupal wing cells. J Cell Biol. 123, 209–221.

50.	Gubb, D. and A. Garcia-Bellido. (1982) A genetic analysis of the determination of cuticular polarity during development in Drosophila melanogaster. J Embryol Exp Morphol. 68, 37–57.

51.	Hall, A. (1998) Rho GTPases and the actin cytoskeleton. Science. 279, 509–514.

52.	Ridley, A.J. and A. Hall. (1992) The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell. 70, 389–399.

53.	Ridley, A.J., H.F. Paterson, C.L. Johnston, D. Diekmann, and A. Hall. (1992) The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell. 70, 401–410.

54.	Boutros, M., N. Paricio, D.I. Strutt, and M. Mlodzik. (1998) Dishevelled activates JNK and discriminates between JNK pathways in planar polarity and wingless signaling. Cell. 94, 109–118.

55.	Zhu, S., L. Liu, V. Korzh, Z. Gong, and B.C. Low. (2006) RhoA acts downstream of Wnt5 and Wnt11 to regulate convergence and extension movements by involving effectors Rho kinase and Diaphanous: use of zebrafish as an in vivo model for GTPase signaling. Cell Signal. 18, 359–372.

56.	Tahinci, E. and K. Symes. (2003) Distinct functions of Rho and Rac are required for convergent extension during Xenopus gas-trulation. Dev Biol. 259, 318–335.

57.	Marlow, F., J. Topczewski, D. Sepich, and L. Solnica-Krezel. (2002) Zebrafish Rho kinase 2 acts downstream of Wnt11 to mediate cell polarity and effective convergence and extension movements. Curr Biol. 12, 876–884.

58.	Winter, C.G., B. Wang, A. Ballew, A. Royou, R. Karess, J.D. Axelrod, et al. (2001) Dro-sophila Rho-associated kinase (Drok) links Frizzled-mediated planar cell polarity signaling to the actin cytoskeleton. Cell. 105, 81–91.

59.	Kim, G.H. and J.K. Han. (2005) JNK and ROKalpha function in the noncanonical Wnt/RhoA signaling pathway to regulate Xenopus convergent extension movements. Dev Dyn. 232, 958–968.

60.	Strutt, D.I., U. Weber, and M. Mlodzik. (1997) The role of RhoA in tissue polarity and Frizzled signalling. Nature. 387, 292–295.

61.	Yamanaka, H., T. Moriguchi, N. Masuyama, M. Kusakabe, H. Hanafusa, R. Takada, et al. (2002) JNK functions in the non-canonical Wnt pathway to regulate convergent extension movements in vertebrates. EMBO Rep. 3, 69–75.

62.	Kohn, A.D. and R.T. Moon. (2005) Wnt and calcium signaling: beta-catenin-inde-pendent pathways. Cell Calcium. 38, 439–446.

63.	Slusarski, D.C. and F. Pelegri. (2007) Calcium signaling in vertebrate embryonic patterning and morphogenesis. Dev Biol. 307, 1–13.

64.	Webb, S.E. and A.L. Miller. (2003) Calcium signalling during embryonic development. Nat Rev Mol Cell Biol. 4, 539–551.

65.	Dejmek, J., A. Safholm, C. Kamp Nielsen, T. Andersson, and K. Leandersson. (2006) Wnt-5a/Ca2+-induced NFAT activity is counteracted by Wnt-5a/Yes-Cdc42-casein kinase 1alpha signaling in human mammary epithelial cells. Mol Cell Biol. 26, 6024– 6036.

66.	Ma, L. and H.Y. Wang. (2006) Suppression of cyclic GMP-dependent protein kinase is essential to the Wnt/cGMP/Ca2+ pathway. J Biol Chem. 281, 30990–31001.

67.	Reinhard, E., H. Yokoe, K.R. Niebling, N.L. Allbritton, M.A. Kuhn, and T. Meyer. (1995) Localized calcium signals in early zebrafish development. Dev Biol. 170, 50–61.

68.	Slusarski, D.C., V.G. Corces, and R.T. Moon. (1997) Interaction of Wnt and a Frizzled homologue triggers G-protein-linked phos-phatidylinositol signalling. Nature. 390, 410–413.

69.	Slusarski, D.C., J. Yang-Snyder, W.B. Busa, and R.T. Moon. (1997) Modulation of embryonic intracellular Ca2+ signaling by Wnt-5A. Dev Biol. 182, 114–120.

70.	Gilland, E., A.L. Miller, E. Karplus, R. Baker, and S.E. Webb. (1999) Imaging of multicellular large-scale rhythmic calcium waves during zebrafish gastrulation. Proc Natl Acad Sci U S A. 96, 157–161.

71.	Wallingford, J.B., A.J. Ewald, R.M. Harland, and S.E. Fraser. (2001) Calcium signaling during convergent extension in Xenopus. Curr Biol. 11, 652–661.

72.	Westfall, T.A., R. Brimeyer, J. Twedt, J. Gladon, A. Olberding, M. Furutani-Seiki, et al. (2003) Wnt-5/pipetail functions in vertebrate axis formation as a negative regulator of Wnt/beta-catenin activity. J Cell Biol. 162, 889–898.

73.	Kuhl, M., L.C. Sheldahl, C.C. Malbon, and R.T. Moon. (2000) Ca(2+)/calmodulin-dependent protein kinase II is stimulated by Wnt and Frizzled homologs and promotes ventral cell fates in Xenopus. J Biol Chem. 275, 12701–12711.

74.	Sheldahl, L.C., D.C. Slusarski, P. Pandur, J.R. Miller, M. Kuhl, and R.T. Moon. (2003) Dishevelled activates Ca2+ flux, PKC, and CamKII in vertebrate embryos. J Cell Biol. 161, 769–777.

75.	Sheldahl, L.C., M. Park, C.C. Malbon, and R.T. Moon. (1999) Protein kinase C is differentially stimulated by Wnt and Frizzled homologs in a G-protein-dependent manner. Curr Biol. 9, 695–698.

76.	Saneyoshi, T., S. Kume, Y. Amasaki, and K. Mikoshiba. (2002) The Wnt/calcium pathway activates NF-AT and promotes ventral cell fate in Xenopus embryos. Nature. 417, 295–299.

77.	Westfall, T.A., B. Hjertos, and D.C. Slusarski. (2003) Requirement for intracellular calcium modulation in zebrafish dorsal-ventral patterning. Dev Biol. 259, 380–391.

78.	Gwak, J., M. Cho, S.J. Gong, J. Won, D.E. Kim, E.Y. Kim, et al. (2006) Protein-kinase-C-mediated beta-catenin phosphorylation negatively regulates the Wnt/beta-catenin pathway. J Cell Sci. 119, 4702–4709.

79.	Ishitani, T., S. Kishida, J. Hyodo-Miura, N. Ueno, J. Yasuda, M. Waterman, et al. (2003) The TAK1-NLK mitogen-activated protein kinase cascade functions in the Wnt-5a/Ca(2+) pathway to antagonize Wnt/beta-catenin signaling. Mol Cell Biol. 23, 131–139.

80.	Ishitani, T., J. Ninomiya-Tsuji, and K. Matsumoto. (2003) Regulation of lym-phoid enhancer factor 1/T-cell factor by mitogen-activated protein kinase-related Nemo-like kinase-dependent phosphoryla-tion in Wnt/beta-catenin signaling. Mol Cell Biol. 23, 1379–1389.

81.	Ishitani, T., J. Ninomiya-Tsuji, S. Nagai, M. Nishita, M. Meneghini, N. Barker, et al. (1999) The TAK1-NLK-MAPK-related pathway antagonizes signalling between beta-catenin and transcription factor TCF. Nature. 399, 798–802.

Comments (Loading...)

Post comment/View all comments