Axis determination in Xenopus involves biochemical interactions of axin, glycogen synthase kinase 3 and beta-catenin

Curr Biol. 1998 May 7;8(10):591-4. doi: 10.1016/s0960-9822(98)70229-5.

Abstract

Signaling by the Wnt family of extracellular proteins is critical in a variety of developmental processes in which cell and tissue polarity are established [1-5]. Wnt signal transduction has been studied mostly by the genetic approach in Drosophila and Caenorhabditis elegans [1,2,5], but the biochemical mechanisms involved remain to be elucidated. The Wnt pathway also operates during axis determination in vertebrates [3,5]. Frizzled receptors transduce a signal to Dishevelled, leading to inactivation of glycogen synthase kinase 3 (GSK3) and regulation of gene expression by the complex of beta-catenin with LEF/TCF (lymphocyte enhancer factor/T-cell factor) transcription factors [3,5]. Axin is a negative regulator of Wnt signaling and dorsal axial development in vertebrates [6]. Here, we demonstrate that axin is associated with GSK3 in the Xenopus embryo and we localize the GSK3-binding domain to a short region of axin. Binding of GSK3 correlates with the ability of axin to inhibit axial development and with the axis-inducing activity of its dominant-negative form (delta RGS). We also find that wild-type axin, but not delta RGS, forms a complex with beta-catenin. Thus, axin may act as a docking station mediating negative regulation of beta-catenin by GSK3 during dorsoventral axis determination in vertebrate embryos.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Axin Protein
  • Axis, Cervical Vertebra / embryology*
  • Binding Sites
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cytoskeletal Proteins / metabolism*
  • Female
  • Glycogen Synthase Kinase 3
  • Glycogen Synthase Kinases
  • Myelin Basic Protein / metabolism
  • Phosphorylation
  • Proteins / genetics
  • Proteins / metabolism*
  • Repressor Proteins*
  • Trans-Activators*
  • Xenopus / embryology
  • Xenopus Proteins
  • beta Catenin

Substances

  • Axin Protein
  • CTNNB1 protein, Xenopus
  • Cytoskeletal Proteins
  • Myelin Basic Protein
  • Proteins
  • Repressor Proteins
  • Trans-Activators
  • Xenopus Proteins
  • axin1 protein, Xenopus
  • beta Catenin
  • Glycogen Synthase Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Glycogen Synthase Kinase 3