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Published online
doi:10.1083/jcb.200710188
The Journal of Cell Biology, Vol. 182, No. 6, 1073-1082
The Rockefeller University Press, 0021-9525 $30.00
© Kim et al.
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Ryk cooperates with Frizzled 7 to promote Wnt11-mediated endocytosis and is essential for Xenopus laevis convergent extension movements



Gun-Hwa Kim, Jung-Hyun Her, and Jin-Kwan Han

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

Correspondence to Jin-Kwan Han: jkh{at}postech.ac.kr

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 β-arrestin 2 (βarr2)-dependent endocytic process triggered by noncanonical Wnt signaling. During X. laevis gastrulation, βarr2-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 βarr2, 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.

Abbreviations used in this paper: βarr2, β-arrestin 2; Cav, caveolin; CE, convergent extension; Co, control; DMZ, dorsal marginal zone; Dsh, dishevelled; Fz, Frizzled; JNK, Jun N-terminal kinase; MO, morpholino oligonucleotide; ORF, open reading frame; PCP, planar cell polarity; Ryk, atypical receptor related tyrosine kinase; XRyk, Xenopus laevis Ryk.

© 2008 Kim et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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