Rap2 is required for Wnt/beta-catenin signaling pathway in Xenopus early development.
The Wnt/beta-catenin signaling pathway is critical for the establishment of organizer and embryonic body axis in Xenopus development. Here, we present evidence that Xenopus Rap2, a member of Ras GTPase family, is implicated in Wnt/beta-catenin signaling during the dorsoventral axis specification. Ectopic expression of XRap2 can lead to neural induction without mesoderm differentiation. XRap2 dorsalizes ventral tissues, inducing axis duplication, organizer-specific gene expression and convergent extension movements. Knockdown of XRap2 causes ventralized phenotypes including shortened body axis and defective dorsoanterior patterning, which are associated with aberrant Wnt signaling. In line with this, XRap2 depletion inhibits beta-catenin stabilization and the induction of ectopic dorsal axis and Wnt-responsive genes caused by XWnt8, Dsh or beta-catenin, but has no effect on the signaling activities of a stabilized beta-catenin. Its knockdown also disrupts the vesicular localization of Dsh, thereby inhibiting Dsh-mediated beta-catenin stabilization and the membrane recruitment and phosphorylation of Dsh by frizzled signaling. Taking together, we suggest that XRap2 is involved in Wnt/beta-catenin signaling as a modulator of the subcellular localization of Dsh.
Choi
Sun-Cheol
SC
Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk, South Korea.
Han
Jin-Kwan
JK
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001483:Base Sequence; D019521:Body Patterning; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D000072261:Dishevelled Proteins; D018507:Gene Expression Regulation, Developmental; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage / Q000235:genetics; D010750:Phosphoproteins / Q000378:metabolism; D015398:Signal Transduction; D013347:Subcellular Fractions / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D051153:Wnt Proteins; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin; D020668:rap GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C495266:CTNNB1 protein, Xenopus; D003598:Cytoskeletal Proteins; C000606586:DVL1 protein, Xenopus; D000072261:Dishevelled Proteins; D036341:Intercellular Signaling Peptides and Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D010750:Phosphoproteins; D015534:Trans-Activators; D051153:Wnt Proteins; D029867:Xenopus Proteins; D051176:beta Catenin; C530501:RAP2A protein, Xenopus; D020668:rap GTP-Binding Proteins