Distinct PAR-1 proteins function in different branches of Wnt signaling during vertebrate development.
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.
Ossipova
Olga
O
Department of Cancer Biology, Dana Farber Cancer Institute, Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Dhawan
Sangeeta
S
Sokol
Sergei
S
Green
Jeremy B A
JB
D000818:Animals; D030801:Animals, Genetically Modified; D001345:Autoradiography / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D019521:Body Patterning / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000378:metabolism; D017403:In Situ Hybridization / Q000379:methods; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases; D008156:Luciferases / Q000378:metabolism; D008845:Microinjections / Q000379:methods; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010641:Phenotype; D010766:Phosphorylation; D014176:Protein Biosynthesis / Q000187:drug effects / Q000502:physiology; D020033:Protein Isoforms / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000172:deficiency / Q000502:physiology*; D012313:RNA / Q000138:chemical synthesis; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D046509:Tissue Culture Techniques; D015534:Trans-Activators / Q000378:metabolism; D051153:Wnt Proteins; D014981:Xenopus; D029867:Xenopus Proteins / Q000737:chemistry / Q000172:deficiency / Q000502:physiology*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin
C495266:CTNNB1 protein, Xenopus; D003598:Cytoskeletal Proteins; D036341:Intercellular Signaling Peptides and Proteins; D016376:Oligonucleotides, Antisense; D020033:Protein Isoforms; D015534:Trans-Activators; D051153:Wnt Proteins; D029867:Xenopus Proteins; D051176:beta Catenin; D049452:Green Fluorescent Proteins; D012313:RNA; D008156:Luciferases; C496647:MARK3 protein, Xenopus; D017346:Protein Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases