Distinct PAR-1 proteins function in different branches of Wnt signaling during vertebrate development

Dev Cell. 2005 Jun;8(6):829-41. doi: 10.1016/j.devcel.2005.04.011.

Abstract

The kinase PAR-1 plays conserved roles in cell polarity. PAR-1 has also been implicated in axis establishment in C. elegans and Drosophila and in Wnt signaling, but its role in vertebrate development is unclear. Here we report that PAR-1 has two distinct and essential roles in axial development in Xenopus mediated by different PAR-1 isoforms. Depletion of PAR-1A or PAR-1BX causes dorsoanterior deficits, reduced Spemann organizer gene expression, and inhibition of canonical Wnt-beta-catenin signaling. By contrast, PAR-1BY depletion inhibits cell movements and localization of Dishevelled protein to the cell cortex, processes associated with noncanonical Wnt signaling. PAR-1 phosphorylation sites in Dishevelled are required for this translocation, but not for canonical Wnt signaling. We conclude that PAR-1BY is required in the PCP branch and mediates Dsh membrane localization while PAR-1A and PAR-1BX are essential for canonical signaling to beta-catenin, possibly via targets other than Dishevelled.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Autoradiography / methods
  • Blotting, Western / methods
  • Body Patterning / physiology
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cytoskeletal Proteins / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Gene Expression Regulation, Developmental* / drug effects
  • Green Fluorescent Proteins / metabolism
  • In Situ Hybridization / methods
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • JNK Mitogen-Activated Protein Kinases
  • Luciferases / metabolism
  • Microinjections / methods
  • Oligonucleotides, Antisense / pharmacology
  • Phenotype
  • Phosphorylation
  • Protein Biosynthesis / drug effects
  • Protein Biosynthesis / physiology
  • Protein Isoforms / metabolism
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / deficiency
  • Protein-Serine-Threonine Kinases / physiology*
  • RNA / chemical synthesis
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Tissue Culture Techniques
  • Trans-Activators / metabolism
  • Wnt Proteins
  • Xenopus
  • Xenopus Proteins / chemistry
  • Xenopus Proteins / deficiency
  • Xenopus Proteins / physiology*
  • Xenopus laevis / embryology*
  • Xenopus laevis / genetics
  • Xenopus laevis / metabolism*
  • beta Catenin

Substances

  • CTNNB1 protein, Xenopus
  • Cytoskeletal Proteins
  • Intercellular Signaling Peptides and Proteins
  • Oligonucleotides, Antisense
  • Protein Isoforms
  • Trans-Activators
  • Wnt Proteins
  • Xenopus Proteins
  • beta Catenin
  • Green Fluorescent Proteins
  • RNA
  • Luciferases
  • MARK3 protein, Xenopus
  • Protein-Serine-Threonine Kinases
  • JNK Mitogen-Activated Protein Kinases