title: Retinoic acid-inducible G protein-coupled receptors bind to frizzled receptors and may activate non-canonical Wnt signaling.
abstract: 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.
authors.affiliation: Neurobiology Program, Children's Hospital Boston, Department of Neurology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Harada
authors.forename: Chika
authors.initials: C
authors.lastname: Yokota
authors.forename: Raymond
authors.initials: R
authors.lastname: Habas
authors.forename: Diane C
authors.initials: DC
authors.lastname: Slusarski
authors.forename: Xi
authors.initials: X
authors.lastname: He
mesh_terms: D000818:Animals; D047108:Embryonic Development / Q000187:drug effects / Q000502:physiology; D051157:Frizzled Receptors / Q000378:metabolism*; D011485:Protein Binding; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology*; D051153:Wnt Proteins / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology* / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism*
chemical_list: D051157:Frizzled Receptors; D043562:Receptors, G-Protein-Coupled; D051153:Wnt Proteins; D014212:Tretinoin