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???displayArticle.abstract??? Dishevelled (Dsh) is a key signaling molecule in the canonical Wnt pathway. Although the mechanism by which Dsh transduces a Wnt signal remains elusive, the subcellular localization of Dsh may be critical for its function. In the early sea urchin embryo, Dsh is concentrated in punctate structures within the cytoplasm of vegetal blastomeres. In these cells, Dsh stabilizes beta-catenin and causes it to accumulate in nuclei, resulting in the activation of transcriptional gene regulatory networks that drive mesoderm and endoderm formation. Here, we present a systematic mutational analysis of Lytechinus variegatus Dsh (LvDsh) that identifies motifs required for its vegetal cortical localization (VCL). In addition to a previously identified lipid-binding motif near the N-terminus of Dsh (Weitzel, H.E., Illies, M.R., Byrum, C.A., Xu, R., Wikramanayake, A.H., Ettensohn, C.A., 2004. Differential stability of beta-catenin along the animal-vegetal axis of the sea urchin embryo mediated by dishevelled. Development 131, 2947-56), we identify a short (21 amino acid) motif between the PDZ and DEP domains that is required for VCL. Phosphorylation of threonine residues in this region regulates both the targeting and stability of LvDsh. We also identify functional nuclear import and export signals within LvDsh. We provide additional evidence that LvDsh is active locally in the vegetal region of the embryo but is inactive in animal blastomeres and show that the inability of LvDsh to function in animal cells is not a consequence of impaired nuclear import. The DIX domain of LvDsh functions as a potent dominant negative when overexpressed (Weitzel, H.E., Illies, M.R., Byrum, C.A., Xu, R., Wikramanayake, A.H., Ettensohn, C.A., 2004. Differential stability of beta-catenin along the animal-vegetal axis of the sea urchin embryo mediated by dishevelled. Development 131, 2947-56). Here, we show that the dominant negative effect of DIX is dependent on a highly conserved, lipid-binding motif that includes residues K57 and E58. The dominant negative effect of DIX is not a consequence of blocking VCL or the nuclear import of LvDsh. We provide evidence that isolated DIX domains interact with full-length LvDsh in vivo. In addition, we show that the K57/E58 lipid-binding motif of DIX is essential for this interaction. We propose that binding of the isolated DIX domain to full-length Dsh may be facilitated by interactions with lipids, and that this interaction may inhibit signaling by a) preventing endogenous Dsh from interacting with Axin, or b) blocking the ability of Dsh to recruit other proteins, such as GBP/Frat1, to the beta-catenin degradation complex.
Aberle,
beta-catenin is a target for the ubiquitin-proteasome pathway.
1997, Pubmed
Aberle,
beta-catenin is a target for the ubiquitin-proteasome pathway.
1997,
Pubmed Amit,
Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway.
2002,
Pubmed Angerer,
Animal-vegetal axis patterning mechanisms in the early sea urchin embryo.
2000,
Pubmed
,
Echinobase Axelrod,
Differential recruitment of Dishevelled provides signaling specificity in the planar cell polarity and Wingless signaling pathways.
1998,
Pubmed Boutros,
Dishevelled activates JNK and discriminates between JNK pathways in planar polarity and wingless signaling.
1998,
Pubmed Boutros,
Dishevelled: at the crossroads of divergent intracellular signaling pathways.
1999,
Pubmed Cadigan,
Wnt signaling: a common theme in animal development.
1997,
Pubmed Capelluto,
Secondary structure, 1H, 13C and 15N resonance assignments and molecular interactions of the dishevelled DIX domain.
2005,
Pubmed Capelluto,
The DIX domain targets dishevelled to actin stress fibres and vesicular membranes.
2002,
Pubmed Chang,
DSH-2 regulates asymmetric cell division in the early C. elegans somatic gonad.
2005,
Pubmed Cheers,
Rapid microinjection of fertilized eggs.
2004,
Pubmed
,
Echinobase Cheyette,
Dapper, a Dishevelled-associated antagonist of beta-catenin and JNK signaling, is required for notochord formation.
2002,
Pubmed Choi,
Rap2 is required for Wnt/beta-catenin signaling pathway in Xenopus early development.
2005,
Pubmed Ciani,
A divergent canonical WNT-signaling pathway regulates microtubule dynamics: dishevelled signals locally to stabilize microtubules.
2004,
Pubmed Cliffe,
A role of Dishevelled in relocating Axin to the plasma membrane during wingless signaling.
2003,
Pubmed Cong,
Casein kinase Iepsilon modulates the signaling specificities of dishevelled.
2004,
Pubmed Dan,
CELL CYCLE STUDY UP TO THE TIME OF HATCHING IN THE EMBRYOS OF THE SEA URCHIN, HEMICENTROTUS PULCHERRIMUS.
1980,
Pubmed
,
Echinobase Davidson,
Lineage-specific gene expression and the regulative capacities of the sea urchin embryo: a proposed mechanism.
1989,
Pubmed
,
Echinobase Dickinson,
The role of Wnt genes in vertebrate development.
1992,
Pubmed Emily-Fenouil,
GSK3beta/shaggy mediates patterning along the animal-vegetal axis of the sea urchin embryo.
1998,
Pubmed
,
Echinobase Ettensohn,
The emergence of pattern in embryogenesis: regulation of beta-catenin localization during early sea urchin development.
2006,
Pubmed
,
Echinobase Fagotto,
Domains of axin involved in protein-protein interactions, Wnt pathway inhibition, and intracellular localization.
1999,
Pubmed Ferkey,
Glycogen synthase kinase-3 beta mutagenesis identifies a common binding domain for GBP and Axin.
2002,
Pubmed Gloy,
Frodo interacts with Dishevelled to transduce Wnt signals.
2002,
Pubmed Greco,
Dishevelled-2 maps to human chromosome 17 and distal to Wnt3a and vestigial tail (vt) on mouse chromosome 11.
1996,
Pubmed Guger,
A mode of regulation of beta-catenin signaling activity in Xenopus embryos independent of its levels.
2000,
Pubmed Habas,
Coactivation of Rac and Rho by Wnt/Frizzled signaling is required for vertebrate gastrulation.
2003,
Pubmed Hart,
Downregulation of beta-catenin by human Axin and its association with the APC tumor suppressor, beta-catenin and GSK3 beta.
1998,
Pubmed Heasman,
Overexpression of cadherins and underexpression of beta-catenin inhibit dorsal mesoderm induction in early Xenopus embryos.
1994,
Pubmed Henderson,
The ins and outs of APC and beta-catenin nuclear transport.
2002,
Pubmed Hino,
Casein kinase I epsilon enhances the binding of Dvl-1 to Frat-1 and is essential for Wnt-3a-induced accumulation of beta-catenin.
2003,
Pubmed Huang,
Constitutive activation of Mek1 by mutation of serine phosphorylation sites.
1994,
Pubmed Huelsken,
The Wnt signalling pathway.
2002,
Pubmed Imai,
(beta)-catenin mediates the specification of endoderm cells in ascidian embryos.
2000,
Pubmed Itoh,
Interaction of dishevelled and Xenopus axin-related protein is required for wnt signal transduction.
2000,
Pubmed Itoh,
Nuclear localization is required for Dishevelled function in Wnt/beta-catenin signaling.
2005,
Pubmed Julius,
Domains of axin and disheveled required for interaction and function in wnt signaling.
2000,
Pubmed Kelly,
Maternally controlled (beta)-catenin-mediated signaling is required for organizer formation in the zebrafish.
2000,
Pubmed Kimelman,
beta-catenin destruction complex: insights and questions from a structural perspective.
2006,
Pubmed Kishida,
DIX domains of Dvl and axin are necessary for protein interactions and their ability to regulate beta-catenin stability.
1999,
Pubmed Klingensmith,
The Drosophila segment polarity gene dishevelled encodes a novel protein required for response to the wingless signal.
1994,
Pubmed Klingensmith,
Conservation of dishevelled structure and function between flies and mice: isolation and characterization of Dvl2.
1996,
Pubmed Krasnow,
Dishevelled is a component of the frizzled signaling pathway in Drosophila.
1995,
Pubmed Krylova,
Dishevelled-1 regulates microtubule stability: a new function mediated by glycogen synthase kinase-3beta.
2000,
Pubmed Larabell,
Establishment of the dorso-ventral axis in Xenopus embryos is presaged by early asymmetries in beta-catenin that are modulated by the Wnt signaling pathway.
1997,
Pubmed Latres,
The human F box protein beta-Trcp associates with the Cul1/Skp1 complex and regulates the stability of beta-catenin.
1999,
Pubmed Lee,
The roles of APC and Axin derived from experimental and theoretical analysis of the Wnt pathway.
2003,
Pubmed Lee,
Molecular links between X-inactivation and autosomal imprinting: X-inactivation as a driving force for the evolution of imprinting?
2003,
Pubmed Li,
Axin and Frat1 interact with dvl and GSK, bridging Dvl to GSK in Wnt-mediated regulation of LEF-1.
1999,
Pubmed Liu,
beta-Trcp couples beta-catenin phosphorylation-degradation and regulates Xenopus axis formation.
1999,
Pubmed Liu,
Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism.
2002,
Pubmed Logan,
Nuclear beta-catenin is required to specify vegetal cell fates in the sea urchin embryo.
1999,
Pubmed
,
Echinobase Logan,
The Wnt signaling pathway in development and disease.
2004,
Pubmed Miller,
Establishment of the dorsal-ventral axis in Xenopus embryos coincides with the dorsal enrichment of dishevelled that is dependent on cortical rotation.
1999,
Pubmed Mlodzik,
Planar polarity in the Drosophila eye: a multifaceted view of signaling specificity and cross-talk.
1999,
Pubmed Moon,
The promise and perils of Wnt signaling through beta-catenin.
2002,
Pubmed Moriguchi,
Distinct domains of mouse dishevelled are responsible for the c-Jun N-terminal kinase/stress-activated protein kinase activation and the axis formation in vertebrates.
1999,
Pubmed Nasevicius,
Evidence for a frizzled-mediated wnt pathway required for zebrafish dorsal mesoderm formation.
1998,
Pubmed Nusse,
Wnt genes.
1992,
Pubmed Ossipova,
Distinct PAR-1 proteins function in different branches of Wnt signaling during vertebrate development.
2005,
Pubmed Pelegri,
Function of zebrafish beta-catenin and TCF-3 in dorsoventral patterning.
1998,
Pubmed Penton,
A mutational analysis of dishevelled in Drosophila defines novel domains in the dishevelled protein as well as novel suppressing alleles of axin.
2002,
Pubmed Peters,
Casein kinase I transduces Wnt signals.
1999,
Pubmed Pizzuti,
cDNA characterization and chromosomal mapping of two human homologues of the Drosophila dishevelled polarity gene.
1996,
Pubmed Pizzuti,
Human homologue sequences to the Drosophila dishevelled segment-polarity gene are deleted in the DiGeorge syndrome.
1996,
Pubmed Roeser,
Nuclear beta-catenin and the development of bilateral symmetry in normal and LiCl-exposed chick embryos.
1999,
Pubmed Rothbächer,
Dishevelled phosphorylation, subcellular localization and multimerization regulate its role in early embryogenesis.
2000,
Pubmed Salic,
Control of beta-catenin stability: reconstitution of the cytoplasmic steps of the wnt pathway in Xenopus egg extracts.
2000,
Pubmed Schneider,
Beta-catenin translocation into nuclei demarcates the dorsalizing centers in frog and fish embryos.
1996,
Pubmed Schwarz-Romond,
The Wnt signalling effector Dishevelled forms dynamic protein assemblies rather than stable associations with cytoplasmic vesicles.
2005,
Pubmed Shulman,
Frizzled signaling and the developmental control of cell polarity.
1998,
Pubmed Simons,
Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways.
2005,
Pubmed Smalley,
Dishevelled (Dvl-2) activates canonical Wnt signalling in the absence of cytoplasmic puncta.
2005,
Pubmed Smalley,
Interaction of axin and Dvl-2 proteins regulates Dvl-2-stimulated TCF-dependent transcription.
1999,
Pubmed Sodergren,
The genome of the sea urchin Strongylocentrotus purpuratus.
2006,
Pubmed
,
Echinobase Sokol,
Dorsalizing and neuralizing properties of Xdsh, a maternally expressed Xenopus homolog of dishevelled.
1995,
Pubmed Sokol,
Analysis of Dishevelled signalling pathways during Xenopus development.
1996,
Pubmed Strutt,
Frizzled signalling and cell polarisation in Drosophila and vertebrates.
2003,
Pubmed Summers,
A Stereometric Analysis of Karyokinesis, Cytokinesis and Cell Arrangements during and following Fourth Cleavage Period in the Sea Urchin, Lytechinus variegatus: (sea urchin embryo/cell division patterns/stereo imaging/3-D reconstruction).
1993,
Pubmed
,
Echinobase Sun,
PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt signalling.
2001,
Pubmed Sussman,
Isolation and characterization of a mouse homolog of the Drosophila segment polarity gene dishevelled.
1994,
Pubmed Tao,
Maternal wnt11 activates the canonical wnt signaling pathway required for axis formation in Xenopus embryos.
2005,
Pubmed Theisen,
dishevelled is required during wingless signaling to establish both cell polarity and cell identity.
1994,
Pubmed Tomlinson,
Linking Frizzled and Wnt signaling in Drosophila development.
1997,
Pubmed Torres,
Colocalization and redistribution of dishevelled and actin during Wnt-induced mesenchymal morphogenesis.
2000,
Pubmed Tsang,
Isolation and characterization of mouse dishevelled-3.
1996,
Pubmed Vonica,
TCF is the nuclear effector of the beta-catenin signal that patterns the sea urchin animal-vegetal axis.
2000,
Pubmed
,
Echinobase Weitzel,
Differential stability of beta-catenin along the animal-vegetal axis of the sea urchin embryo mediated by dishevelled.
2004,
Pubmed
,
Echinobase Wharton,
Runnin' with the Dvl: proteins that associate with Dsh/Dvl and their significance to Wnt signal transduction.
2003,
Pubmed Wikramanayake,
beta-Catenin is essential for patterning the maternally specified animal-vegetal axis in the sea urchin embryo.
1998,
Pubmed
,
Echinobase Wikramanayake,
An ancient role for nuclear beta-catenin in the evolution of axial polarity and germ layer segregation.
2003,
Pubmed Willert,
Casein kinase 2 associates with and phosphorylates dishevelled.
1997,
Pubmed Wodarz,
Mechanisms of Wnt signaling in development.
1998,
Pubmed Wong,
Direct binding of the PDZ domain of Dishevelled to a conserved internal sequence in the C-terminal region of Frizzled.
2003,
Pubmed Yanagawa,
Casein kinase I phosphorylates the Armadillo protein and induces its degradation in Drosophila.
2002,
Pubmed Yanagawa,
The dishevelled protein is modified by wingless signaling in Drosophila.
1995,
Pubmed Yang-Snyder,
A frizzled homolog functions in a vertebrate Wnt signaling pathway.
1996,
Pubmed Yost,
GBP, an inhibitor of GSK-3, is implicated in Xenopus development and oncogenesis.
1998,
Pubmed Yost,
The axis-inducing activity, stability, and subcellular distribution of beta-catenin is regulated in Xenopus embryos by glycogen synthase kinase 3.
1996,
Pubmed Zeng,
The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation.
1997,
Pubmed
