| Budget Amount *help |
¥45,760,000 (Direct Cost: ¥35,200,000、Indirect Cost: ¥10,560,000)
Fiscal Year 2017: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2016: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2015: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2014: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2013: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
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| Outline of Final Research Achievements |
Wnt proteins direct embryonic patterning as a morphogen, but the regulatory basis of their distribution and signal reception remain unclear. In this project, we show that the Wnt8 protein is accumulated on the cell surface in a punctate manner in association with “N-sulfo heparan sulfate (HS),” not with “N-acetyl HS”. These two types of HS are differentially clustered by attaching to different types of glypicans, Gpc4 and Gpc5 as core proteins. N-sulfo HS is frequently internalized and associated with the signaling vesicle, known as the Frizzled/Wnt/LRP6 signalosome. Conversely, N-acetyl HS is rarely internalized and accumulates Frzb, a secreted Wnt antagonist. Upon interaction with Frzb, Wnt8 associates with N-acetyl HS, suggesting that N-acetyl HS supports Frzb-mediated antagonism by sequestering Wnt8 from N-sulfo HS. Thus, these two types of HS clusters may constitute a cellular platform for the distribution and signaling of Wnt8.
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