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    Biochem Biophys Res Commun. 2007 Jul 13;358(4):968-75. Epub 2007 May 11.

    Retinoic acid-inducible G protein-coupled receptors bind to frizzled receptors and may activate non-canonical Wnt signaling.

    Harada Y, Yokota C, Habas R, Slusarski DC, He X.

    Neurobiology Program, Children's Hospital Boston, Department of Neurology, Harvard Medical School, Boston, MA 02115, USA.

    Frizzled (Fz) seven-pass transmembrane receptors are Wnt receptors and function in a variety of developmental pathways. Here we identify retinoic acid-inducible gene-1, 2, 3, and 4 (RAIG1, 2, 3, and 4) as potential Fz binding proteins. RAIG proteins are seven-pass transmembrane receptors, and Xenopus RAIG2, 3, and 4 are expressed in early gastrula. XRAIG2 can activate small GTPases, such as RhoA, Rac, and Cdc42, and c-jun N-terminal kinase, thus exhibit activities that overlap with non-canonical Wnt/Fz signaling. Injection of XRAIG2 mRNA into Xenopus embryo causes a severe shortened and bent body axis due to defective gastrulation movements, reminiscent of abnormal non-canonical Wnt signaling. XRAIG2 affects convergent extension in activin-treated animal caps, which can be partially rescued by co-injection of a dominant-negative form of Cdc42. In zebrafish embryo, XRAIG2 also causes Ca(2+) flux, one of the consequences of non-canonical Wnt signaling. These results suggest a possible crosstalk/integration between Wnt/Frizzled and RAIG signal transduction pathways.

    PMID: 17521608 [PubMed - indexed for MEDLINE]

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