2013 Fiscal Year Final Research Report
Selective activation of Wnt signaling pathway using with purified Wnt proteins
| Project/Area Number |
23590333
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Osaka University |
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Principal Investigator |
YAMAMOTO Hideki 大阪大学, 医学(系)研究科(研究院), 准教授 (20372691)
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| Co-Investigator(Renkei-kenkyūsha) |
TAKAO Toshifumi 大阪大学, 蛋白質研究所, 教授 (10197048)
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| Project Period (FY) |
2011 – 2013
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| Keywords | Wntシグナル経路 / Wnt / 受容体 / 翻訳後修飾 / 細胞内小胞輸送 |
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| Research Abstract |
Wnts are glycan- and lipid-modified morphogens that are important for cellular responses, but how Wnt is secreted in polarized epithelial cells remains unclear. Here we show the apicobasal secretion of Wnts is regulated by different mechanisms. Wnt11 and Wnt3a were secreted apically and basolaterally, respectively, in polarized epithelial cells. Wntless was localized to the basolateral membrane. Mass-spectrometric analyses revealed that Wnt11 is modified with complex/hybrid-(Asn40), high-mannose-(Asn90), and high-mannose/hybrid-(Asn300) type glycans and that Wnt3a is modified with two high-mannose-type glycans (Asn87 and Asn298). Glycosylation processing at Asn40 and galectin-3 were required for the apical secretion of Wnt11, while clathrin and adaptor protein-1 were required for the basolateral secretion of Wnt3a. These results suggest that Wls has different roles on the polarized secretion of Wnt11 and Wnt3a and that glycosylation processing of Wnts decides their secretory routes
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[Journal Article] Apical and basolateral secretion of Wnt11 and Wnt3a in polarized epithelial cells is regulated by different mechanisms2013
Author(s)
Yamamoto, H., Awada, C., Hanaki, H., Sakane, H., Tsujimoto, I., Takahashi, Y., Takao, T., Kikuchi, A.
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Journal Title
J. Cell Sci.
Volume: 126
Pages: 2931-2943
DOI
Peer Reviewed
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[Journal Article] An anti-Wnt5a antibody suppresses metastasis of gastric cancer cells in vivo by inhibiting receptor-mediated endocytosis2012
Author(s)
Hanaki, H., Yamamoto, H., Sakane, H., Matsumoto, S., Ohdan, H., Sato, A., Kikuchi, A.
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Journal Title
Mol. Cancer Tehr.
Volume: 11
Pages: 298-307
DOI
Peer Reviewed
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[Journal Article] The transmembrane protein Waif1/5T4 inhibits Wnt/β-catenin signaling and activates noncanonical Wnt pathways by modifying LRP6 subcellular localization2011
Author(s)
Kagermeier-Schenk, B., Wehner, D., Ö z h a n -Kizil, G. Yamamoto, H., Li, J., Kirchner, K., Hoffmann, C., Stern, P., Kikuchi, A., Schambony, A., Weidinger, G.
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Journal Title
Dev. Cell
Volume: 21
Pages: 1129-1143
DOI
Peer Reviewed
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