Analysis of Wnt signaling pathway mediated frizzled protein family

Wnt信号通路介导的卷曲蛋白家族分析

• 批准号: 13680795
• 负责人: YAO Ryoji
• 金额: $ 2.24万
• 依托单位: Japanese Foundation for Cancer Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13680795/
• 关键词: frizzled; Wnt; GOPC; veslcle transport; wnt; Vesicle transport; PDZ domain; 細胞分裂

Frizzled proteins play a role as a Wnt receptor and involved in the regulation of gene expression as well as planar cell polarity. Since carboxyl temini of many frizzled family members contain PDZ binding motifs, we isolated several candidate molecules that potentially interact with frizzled.One of these interacting proteins, fzip-1 , contains two coiled-coil motif and one PDZ domain. This molecule was named as Golgi-associated PDZ and coiled-coil motif containing protein (GOPC), as it was localized at the Golgi apparatus. A series of molecular studies indicates GOPC has a role in transport of frizzled form the Golgi apparatus to plasma membrane. Furthermore, Male GOPC knockout mouse was infertile due to abnormal acrosome formation. Electronmicrosopic analysis revealed that vesicle transport from the Golgi apparatus to acrosome was severely impaired. Thus it appears GOPC functions the vesicle transport to acrosome in addition to plasma membrane. We also found that the second interacting molecule; fzip-2, is involved in G protein dependent -JNK activation, whereas the third molecule, fzip-3, is suggested to function in cell division. We are currently investigating the molecular analysis of these molecules as well as their biological significance by gene targeting.

卷曲蛋白发挥 Wnt 受体的作用，参与基因表达和平面细胞极性的调节。由于许多 frizzled 家族成员的羧基末端含有 PDZ 结合基序，我们分离了几种可能与 frizzled 相互作用的候选分子。这些相互作用蛋白之一 fzip-1 包含两个卷曲螺旋基序和一个 PDZ 结构域。该分子被命名为高尔基相关 PDZ 和含有卷曲螺旋基序的蛋白 (GOPC)，因为它位于高尔基体。一系列分子研究表明 GOPC 在将卷曲从高尔基体转运到质膜中发挥作用。此外，雄性GOPC基因敲除小鼠由于顶体形成异常而无法生育。电子显微镜分析显示，囊泡从高尔基体到顶体的运输严重受损。因此，除了质膜之外，GOPC 还具有将囊泡转运至顶体的功能。我们还发现了第二个相互作用的分子； fzip-2 参与 G 蛋白依赖性 -JNK 激活，而第三个分子 fzip-3 则被认为在细胞分裂中发挥作用。我们目前正在研究这些分子的分子分析及其通过基因靶向的生物学意义。

项目成果

Yao, R., Maeda, T., Takada, S., Noda.T.: "Identification of a PDZ domain containing Golgi protein, GOPC, as an interacting partner of frizzled"Biochem.Biophys.Res.Comm.. 286. 771-778 (2001)

Yao, R.、Maeda, T.、Takada, S.、Noda.T.：“含有高尔基体蛋白 GOPC 的 PDZ 结构域的鉴定，作为卷曲的相互作用伙伴”Biochem.Biophys.Res.Comm.. 286。