Ryk cooperates with Frizzled 7 to promote Wnt11-mediated endocytosis and is essential for Xenopus laevis convergent extension movements.
The single-pass transmembrane protein Ryk (atypical receptor related tyrosine kinase) functions as a Wnt receptor. However, Ryk's correlation with Wnt/Frizzled (Fz) signaling is poorly understood. Here, we report that Ryk regulates Xenopus laevis convergent extension (CE) movements via the beta-arrestin 2 (betaarr2)-dependent endocytic process triggered by noncanonical Wnt signaling. During X. laevis gastrulation, betaarr2-mediated endocytosis of Fz7 and dishevelled (Dvl/Dsh) actually occurs in the dorsal marginal zone tissues, which actively participate in noncanonical Wnt signaling. Noncanonical Wnt11/Fz7-mediated endocytosis of Dsh requires the cell-membrane protein Ryk. Ryk interacts with both Wnt11 and betaarr2, cooperates with Fz7 to mediate Wnt11-stimulated endocytosis of Dsh, and signals the noncanonical Wnt pathway in CE movements. Conversely, depletion of Ryk and Wnt11 prevents Dsh endocytosis in dorsal marginal zone tissues. Our study suggests that Ryk functions as an essential regulator for noncanonical Wnt/Fz-mediated endocytosis in the regulation of X. laevis CE movements.
Kim
Gun-Hwa
GH
Department of Life Science, Division of Molecular and Life Sciences, Pohang University of Science and Technology, Hyoja Dong, Pohang, Kyungbuk 790-784, Republic of Korea.
Her
Jung-Hyun
JH
Han
Jin-Kwan
JK
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D019390:Arrestins / Q000235:genetics / Q000378:metabolism; D019521:Body Patterning; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D000072261:Dishevelled Proteins; D004705:Endocytosis / Q000502:physiology*; D006801:Humans; D009024:Morphogenesis; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000033:anatomy & histology / Q000196:embryology* / Q000378:metabolism; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
C000605254:ARRB2 protein, human; D048868:Adaptor Proteins, Signal Transducing; D019390:Arrestins; C000606586:DVL1 protein, Xenopus; D000072261:Dishevelled Proteins; C492040:Fzd7 protein, Xenopus; D016376:Oligonucleotides, Antisense; D010750:Phosphoproteins; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins; D051153:Wnt Proteins; D029867:Xenopus Proteins; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; C512785:wnt11b protein, Xenopus; D020794:Receptor Protein-Tyrosine Kinases; C532248:Ryk protein, Xenopus; D020742:rhoA GTP-Binding Protein