| 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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| 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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