Regulation of membrane traffic of Wnt and its receptors
| Project/Area Number |
26460365
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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 |
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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) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | Wnt / 受容体 / 小胞輸送 / 翻訳後修飾 / LRP6 / 細胞内トラフィック / LDL / Wntシグナル |
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| Outline of Final Research Achievements |
Mass-spectrometric analyses revealed that Wnt5a and Wnt5b are modified with palmitoleic acid and two high-mannose-type and hybrid-type glycans. We found that Wnt5a is secreted basolaterally and Wnt1 is equivalently secreted both apically and basolaterally in polarized MDCK cells. We also found that Wnt5b is secreted as a soluble form or as an exosome-associated form. The basolateral secretion of Wnt5a and Wnt1 required Wntless (Wls), clathrin and AP-1. Wnt1 was secreted apically via exocyst-mediated transport. Wnt5a receptors were also localized to the basolateral membranes. Knockdown of Wnt5a delayed apical lumen formation of the epithelial cyst, and these phenotypes were rescued by wild-type Wnt5a, but not by a Wnt5a mutant that is secreted apically. These results suggest that Wnt5a and its receptors are sorted to their correct destination by different mechanisms and that the basolateral secretion of Wnt5a is necessary for apical lumen formation in the epithelial cyst.
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Report
(4 results)
Research Products
(15 results)
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[Journal Article] Wnt5b-associated Exosomes promote cell proliferation and migration in a cancer cell context2016
Author(s)
Harada, T., Yamamoto, H., Kishida, S., Kishida, M., Awada, C., Takao, T., and Kikuchi, A.
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Journal Title
Cancer Sci.
Volume: 108
Issue: 1
Pages: 42-52
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Active and water-soluble form of lipidated Wnt protein is maintained by a serum glycoprotein afamin/α-albumin.2016
Author(s)
Mihara, E., Hirai, H., Yamamoto, H., Tamura-Kawakami, K., Matano, M., Kikuchi, A., Sato, T., and Takagi, J.
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Journal Title
Elife
Volume: 5
Pages: 1-19
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A. Basolateral secretion of Wnt5a in polarized epithelial cells is required for apical lumen formation2015
Author(s)
Yamamoto, H., Awada, C., Matsumoto, S., Kaneiwa, T., Sugimoto, T., Takao, T., and Kikuchi
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Journal Title
J. Cell Sci.
Volume: 128
Pages: 1051-1063
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Wnt5a promotes cancer cell invasion and proliferation by receptor-mediated endocytosis-dependent and -independent mechanisms, respectively2015
Author(s)
Shojima, K., Sato, A., Hanaki, H., Tsujimoto, I., Nakamura, M., Hattori, K., Sato, Y., Dohi, K., Hirata, M., Yamamoto, H., and Kikuchi, A.
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Journal Title
Sci. Rep.
Volume: 5
Issue: 1
Pages: 8042-8042
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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