Project/Area Number |
23590333
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
General medical chemistry
|
Research Institution | Osaka University |
Principal Investigator |
YAMAMOTO Hideki 大阪大学, 医学(系)研究科(研究院), 准教授 (20372691)
|
Co-Investigator(Renkei-kenkyūsha) |
TAKAO Toshifumi 大阪大学, 蛋白質研究所, 教授 (10197048)
|
Project Period (FY) |
2011 – 2013
|
Project Status |
Completed (Fiscal Year 2013)
|
Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | Wntシグナル経路 / Wnt / 受容体 / 翻訳後修飾 / 細胞内小胞輸送 / Wntシグナル / Wntless / 糖鎖修飾 / 極性分泌 / クラスリン / AP1 / AP2 / ガレクチン / Wnt11 |
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
|