Axis determination in Xenopus involves biochemical interactions of axin, glycogen synthase kinase 3 and beta-catenin.
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.
Itoh
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K
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts, USA.
Krupnik
V E
VE
Sokol
S Y
SY
D000818:Animals; D060466:Axin Protein; D001368:Axis, Cervical Vertebra / Q000196:embryology*; D001665:Binding Sites; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005260:Female; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D004676:Myelin Basic Protein / Q000378:metabolism; D010766:Phosphorylation; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins; D015534:Trans-Activators; D014981:Xenopus / Q000196:embryology; D029867:Xenopus Proteins; D051176:beta Catenin
D060466:Axin Protein; C495266:CTNNB1 protein, Xenopus; D003598:Cytoskeletal Proteins; D004676:Myelin Basic Protein; D011506:Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D029867:Xenopus Proteins; C555454:axin1 protein, Xenopus; D051176:beta Catenin; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3