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Molecular and Cellular Biology, April 2009, p. 2118-2128, Vol. 29, No. 8
0270-7306/09/$08.00+0     doi:10.1128/MCB.01503-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Xenopus Wntless and the Retromer Complex Cooperate To Regulate XWnt4 Secretion{triangledown}

Hyunjoon Kim,1 Seong-Moon Cheong,1 Jihae Ryu,1 Hwa-Jin Jung,2 Eek-hoon Jho,2 and Jin-Kwan Han1*

Division of Molecular and Life Sciences, Pohang University of Science and Technology, San 31, Hyoja-Dong, Pohang, Kyungbuk 790-784, Republic of Korea,1 Department of Life Science, University of Seoul, Seoul 130-743, Republic of Korea2

Received 25 September 2008/ Returned for modification 27 October 2008/ Accepted 2 February 2009

Wnt signaling is implicated in a variety of developmental and pathological processes. The molecular mechanisms governing the secretion of Wnt ligands remain to be elucidated. Wntless, an evolutionarily conserved multipass transmembrane protein, is a dedicated secretion factor of Wnt proteins that participates in Drosophila melanogaster embryogenesis. In this study, we show that Xenopus laevis Wntless (XWntless) regulates the secretion of a specific Wnt ligand, XWnt4, and that this regulation is specifically required for eye development in Xenopus. Moreover, the Retromer complex is required for XWntless recycling to regulate the XWnt4-mediated eye development. Inhibition of Retromer function by Vps35 morpholino (MO) resulted in various Wnt deficiency phenotypes, affecting mesoderm induction, gastrulation cell movements, neural induction, neural tube closure, and eye development. Overexpression of XWntless led to the rescue of Vps35 MO-mediated eye defects but not other deficiencies. These results collectively suggest that XWntless and the Retromer complex are required for the efficient secretion of XWnt4, facilitating its role in Xenopus eye development.

* Corresponding author. Mailing address: Division of Molecular and Life Sciences, Pohang University of Science and Technology, San 31, Hyoja-Dong, Pohang, Kyungbuk 790-784, Republic of Korea. Phone: 82-54-279-2126. Fax: 82-54-279-2199. E-mail: jkh{at}postech.ac.kr

{triangledown} Published ahead of print on 17 February 2009.

Molecular and Cellular Biology, April 2009, p. 2118-2128, Vol. 29, No. 8
0270-7306/09/$08.00+0     doi:10.1128/MCB.01503-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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