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PMID: 9362521 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Antagonism of cell adhesion by an alpha-catenin mutant, and of the Wnt-signaling pathway by alpha-catenin in Xenopus embryos.

The Journal of cell biology ·Vol. 139 ·No. 4 ·1997-11-17 ·Pages 1033-46

Sehgal RN, Gumbiner BM, Reichardt LF

Abstract

In Xenopus laevis development, beta-catenin plays an important role in the Wnt-signaling pathway by establishing the Nieuwkoop center, which in turn leads to specification of the dorsoventral axis. Cadherins are essential for embryonic morphogenesis since they mediate calcium-dependent cell-cell adhesion and can modulate beta-catenin signaling. alpha-catenin links beta-catenin to the actin-based cytoskeleton. To study the role of endogenous alpha-catenin in early development, we have made deletion mutants of alphaN-catenin. The binding domain of beta-catenin has been mapped to the NH2-terminal 210 amino acids of alphaN-catenin. Overexpression of mutants lacking the COOH-terminal 230 amino acids causes severe developmental defects that reflect impaired calcium-dependent blastomere adhesion. Lack of normal adhesive interactions results in a loss of the blastocoel in early embryos and ripping of the ectodermal layer during gastrulation. The phenotypes of the dominant-negative mutants can be rescued by coexpressing full-length alphaN-catenin or a mutant of beta-catenin that lacks the internal armadillo repeats. We next show that coexpression of alphaN-catenin antagonizes the dorsalizing effects of beta-catenin and Xwnt-8. This can be seen phenotypically, or by studying the effects of expression on the downstream homeobox gene Siamois. Thus, alpha-catenin is essential for proper morphogenesis of the embryo and may act as a regulator of the intracellular beta-catenin signaling pathway in vivo.

MeSH Terms
Animals Calcium/physiology Cell Adhesion Cytoskeletal Proteins/chemistry,physiology Embryonic Induction Gastrula/cytology Gene Expression Regulation, Developmental Genes, Homeobox Homeodomain Proteins/genetics Morphogenesis Protein Binding Proto-Oncogene Proteins/physiology Signal Transduction Structure-Activity Relationship Trans-Activators Wnt Proteins Xenopus Proteins Xenopus laevis/embryology Zebrafish Proteins alpha Catenin beta Catenin
Chemicals
CTNNB1 protein, Xenopus Cytoskeletal Proteins Homeodomain Proteins Proto-Oncogene Proteins SIA1 protein, Xenopus Trans-Activators Wnt Proteins Xenopus Proteins Zebrafish Proteins alpha Catenin beta Catenin wnt8a protein, Xenopus Calcium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Sehgal R N
Cell Biology Program, Department of Biochemistry and Biophysics, and Howard Hughes Medical Institute, University of California, San Francisco, California 94143-0724, USA.
Gumbiner B M
Reichardt L F
References (61)
61 references, click to expand
  1. Functional interaction of beta-catenin with the transcription factor LEF-1.
    Nature. 1996 Aug 15;382(6592):638-42 PMID: 8757136
  2. The axis-inducing activity, stability, and subcellular distribution of beta-catenin is regulated in Xenopus embryos by glycogen synthase kinase 3.
    Genes Dev. 1996 Jun 15;10(12):1443-54 PMID: 8666229
  3. beta-Catenin associates with the actin-bundling protein fascin in a noncadherin complex.
    J Cell Biol. 1996 Sep;134(5):1271-81 PMID: 8794867
  4. Association between a transmembrane protein tyrosine phosphatase and the cadherin-catenin complex.
    J Cell Biol. 1996 Sep;134(6):1519-29 PMID: 8830779
  5. Nuclear localization of beta-catenin by interaction with transcription factor LEF-1.
    Mech Dev. 1996 Sep;59(1):3-10 PMID: 8892228
  6. The entire mesodermal mantle behaves as Spemann's organizer in dorsoanterior enhanced Xenopus laevis embryos.
    Dev Biol. 1988 May;127(1):64-77 PMID: 3282938
  7. The 102 kd cadherin-associated protein: similarity to vinculin and posttranscriptional regulation of expression.
    Cell. 1991 May 31;65(5):849-57 PMID: 1904011
  8. The uvomorulin-anchorage protein alpha catenin is a vinculin homologue.
    Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9156-60 PMID: 1924379
  9. Injected Wnt RNA induces a complete body axis in Xenopus embryos.
    Cell. 1991 Nov 15;67(4):741-52 PMID: 1834344
  10. Injected Xwnt-8 RNA acts early in Xenopus embryos to promote formation of a vegetal dorsalizing center.
    Cell. 1991 Nov 15;67(4):753-65 PMID: 1657405
  11. Regulation of embryonic cell adhesion by the cadherin cytoplasmic domain.
    Cell. 1992 Apr 17;69(2):225-36 PMID: 1568244
  12. Signal transduction through beta-catenin and specification of cell fate during embryogenesis.
    Genes Dev. 1996 Oct 15;10(20):2527-39 PMID: 8895655
  13. The homeobox gene Siamois is a target of the Wnt dorsalisation pathway and triggers organiser activity in the absence of mesoderm.
    Development. 1996 Oct;122(10):3055-65 PMID: 8898219
  14. Cadherins and catenins in development.
    Curr Opin Cell Biol. 1996 Oct;8(5):685-91 PMID: 8939663
  15. Activation of Siamois by the Wnt pathway.
    Dev Biol. 1996 Nov 25;180(1):344-7 PMID: 8948596
  16. Adenomatous polyposis coli tumor suppressor protein has signaling activity in Xenopus laevis embryos resulting in the induction of an ectopic dorsoanterior axis.
    J Cell Biol. 1997 Jan 27;136(2):411-20 PMID: 9015311
  17. Regulation of complexed and free catenin pools by distinct mechanisms. Differential effects of Wnt-1 and v-Src.
    J Biol Chem. 1997 Feb 14;272(7):4536-43 PMID: 9020180
  18. An alpha-E-catenin gene trap mutation defines its function in preimplantation development.
    Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):901-6 PMID: 9023354
  19. Induction of the primary dorsalizing center in Xenopus by the Wnt/GSK/beta-catenin signaling pathway, but not by Vg1, Activin or Noggin.
    Development. 1997 Jan;124(2):453-60 PMID: 9053321
  20. pangolin encodes a Lef-1 homologue that acts downstream of Armadillo to transduce the Wingless signal in Drosophila.
    Nature. 1997 Feb 27;385(6619):829-33 PMID: 9039917
  21. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma.
    Science. 1997 Mar 21;275(5307):1784-7 PMID: 9065401
  22. Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC.
    Science. 1997 Mar 21;275(5307):1787-90 PMID: 9065402
  23. Stabilization of beta-catenin by genetic defects in melanoma cell lines.
    Science. 1997 Mar 21;275(5307):1790-2 PMID: 9065403
  24. LEF-1, a nuclear factor coordinating signaling inputs from wingless and decapentaplegic.
    Cell. 1997 Mar 21;88(6):777-87 PMID: 9118221
  25. Armadillo coactivates transcription driven by the product of the Drosophila segment polarity gene dTCF.
    Cell. 1997 Mar 21;88(6):789-99 PMID: 9118222
  26. Beta-catenin as oncogene: the smoking gun.
    Science. 1997 Mar 21;275(5307):1752-3 PMID: 9122680
  27. The roles of maternal alpha-catenin and plakoglobin in the early Xenopus embryo.
    Development. 1997 Apr;124(8):1553-60 PMID: 9108371
  28. Association of the APC tumor suppressor protein with catenins.
    Science. 1993 Dec 10;262(5140):1734-7 PMID: 8259519
  29. Identification of a neural alpha-catenin as a key regulator of cadherin function and multicellular organization.
    Cell. 1992 Jul 24;70(2):293-301 PMID: 1638632
  30. The armadillo homologs beta-catenin and plakoglobin are differentially expressed during early development of Xenopus laevis.
    Dev Biol. 1992 Oct;153(2):337-46 PMID: 1397690
  31. Catenins in Xenopus embryogenesis and their relation to the cadherin-mediated cell-cell adhesion system.
    Development. 1993 Jun;118(2):629-40 PMID: 8223282
  32. From cadherins to catenins: cytoplasmic protein interactions and regulation of cell adhesion.
    Trends Genet. 1993 Sep;9(9):317-21 PMID: 8236461
  33. Association of the APC gene product with beta-catenin.
    Science. 1993 Dec 10;262(5140):1731-4 PMID: 8259518
  34. Expression of Wnt-1 in PC12 cells results in modulation of plakoglobin and E-cadherin and increased cellular adhesion.
    J Cell Biol. 1993 Dec;123(6 Pt 2):1857-65 PMID: 8276903
  35. Wnt-1 modulates cell-cell adhesion in mammalian cells by stabilizing beta-catenin binding to the cell adhesion protein cadherin.
    J Cell Biol. 1994 Mar;124(5):729-41 PMID: 8120095
  36. Dynamics of cadherin/catenin complex formation: novel protein interactions and pathways of complex assembly.
    J Cell Biol. 1994 Jun;125(6):1327-40 PMID: 8207061
  37. Regulation of C-cadherin function during activin induced morphogenesis of Xenopus animal caps.
    J Cell Biol. 1994 Jul;126(2):519-27 PMID: 8034750
  38. Xenopus embryos regulate the nuclear localization of XMyoD.
    Genes Dev. 1994 Jun 1;8(11):1311-23 PMID: 7926732
  39. The roles of catenins in the cadherin-mediated cell adhesion: functional analysis of E-cadherin-alpha catenin fusion molecules.
    J Cell Biol. 1994 Oct;127(1):235-45 PMID: 7929566
  40. Induction of polarized cell-cell association and retardation of growth by activation of the E-cadherin-catenin adhesion system in a dispersed carcinoma line.
    J Cell Biol. 1994 Oct;127(1):247-56 PMID: 7929567
  41. Differential perturbations in the morphogenesis of anterior structures induced by overexpression of truncated XB- and N-cadherins in Xenopus embryos.
    J Cell Biol. 1994 Oct;127(2):521-35 PMID: 7929592
  42. Overexpression of cadherins and underexpression of beta-catenin inhibit dorsal mesoderm induction in early Xenopus embryos.
    Cell. 1994 Dec 2;79(5):791-803 PMID: 7528101
  43. E-cadherin and APC compete for the interaction with beta-catenin and the cytoskeleton.
    J Cell Biol. 1994 Dec;127(6 Pt 2):2061-9 PMID: 7806582
  44. Embryonic axis induction by the armadillo repeat domain of beta-catenin: evidence for intracellular signaling.
    J Cell Biol. 1995 Mar;128(5):959-68 PMID: 7876319
  45. Regulation of intracellular beta-catenin levels by the adenomatous polyposis coli (APC) tumor-suppressor protein.
    Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):3046-50 PMID: 7708772
  46. Expression cloning of Siamois, a Xenopus homeobox gene expressed in dorsal-vegetal cells of blastulae and able to induce a complete secondary axis.
    Cell. 1995 Apr 7;81(1):85-94 PMID: 7720076
  47. Anterior axis duplication in Xenopus induced by the over-expression of the cadherin-binding protein plakoglobin.
    Proc Natl Acad Sci U S A. 1995 May 9;92(10):4522-6 PMID: 7753837
  48. Genetic and biochemical dissection of protein linkages in the cadherin-catenin complex.
    Proc Natl Acad Sci U S A. 1995 May 23;92(11):5067-71 PMID: 7761449
  49. Interaction of alpha-actinin with the cadherin/catenin cell-cell adhesion complex via alpha-catenin.
    J Cell Biol. 1995 Jul;130(1):67-77 PMID: 7790378
  50. Selective disruption of E-cadherin function in early Xenopus embryos by a dominant negative mutant.
    Development. 1994 Apr;120(4):901-9 PMID: 7600966
  51. Role of glycogen synthase kinase 3 beta as a negative regulator of dorsoventral axis formation in Xenopus embryos.
    Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8498-502 PMID: 7667318
  52. FGF is a prospective competence factor for early activin-type signals in Xenopus mesoderm induction.
    Development. 1995 Aug;121(8):2429-37 PMID: 7671807
  53. Alpha 1(E)-catenin is an actin-binding and -bundling protein mediating the attachment of F-actin to the membrane adhesion complex.
    Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8813-7 PMID: 7568023
  54. Signal transduction of beta-catenin.
    Curr Opin Cell Biol. 1995 Oct;7(5):634-40 PMID: 8573337
  55. Single amino acid substitutions in proteins of the armadillo gene family abolish their binding to alpha-catenin.
    J Biol Chem. 1996 Jan 19;271(3):1520-6 PMID: 8576147
  56. Binding to cadherins antagonizes the signaling activity of beta-catenin during axis formation in Xenopus.
    J Cell Biol. 1996 Mar;132(6):1105-14 PMID: 8601588
  57. Wnt-1 regulates free pools of catenins and stabilizes APC-catenin complexes.
    Mol Cell Biol. 1996 May;16(5):2128-34 PMID: 8628279
  58. Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly.
    Science. 1996 May 17;272(5264):1023-6 PMID: 8638126
  59. Contribution of cadherins to directional cell migration and histogenesis in Xenopus embryos.
    Cell Adhes Commun. 1995 Dec;3(5):419-40 PMID: 8640379
  60. Activities of the Wnt-1 class of secreted signaling factors are antagonized by the Wnt-5A class and by a dominant negative cadherin in early Xenopus development.
    J Cell Biol. 1996 Jun;133(5):1123-37 PMID: 8655584
  61. XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos.
    Cell. 1996 Aug 9;86(3):391-9 PMID: 8756721
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.139.4.1033
Published
1997-11-17
Pages
1033-46
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2139960
Subset
IM
Grants
NIGMS NIH HHS · T32 GM 08120 · United States
External Links
PubMed source DOI: 10.1083/jcb.139.4.1033 PMC Full Text View journal details
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