2016 Fiscal Year Final Research Report
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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| Keywords | Wnt / 受容体 / 小胞輸送 / 翻訳後修飾 |
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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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| Free Research Field |
生化学、細胞生物学
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