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Cell biological functions of phosphoinositides-phosphorylation of 5-position

磷酸肌醇的细胞生物学功能-5位磷酸化

基本信息

批准号：
14580690
负责人：
SHIBASAKI Yoshikazu
金额：
$ 2.3万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14580690/
关键词：
vesicular traffic actin endocytosis inositol kinase cytoskeleton キナーゼ PHドメイン低分子量G蛋白 GFP PIP2

项目摘要

For vesicular traffic, the interaction between molecules on vesicles and cytoplasmic proteins is important. In this study, we focused on phosphoinositides (PI) on the vesicular membrane and its phosphorylation. Phosphorylation of PI is regulated by phosphatidylinositol kinases and phosphatases. Especially, phosphatidylinositol (4,5) bisphosphate (PIP2) is important for membrane traffic. The final step of PIP2 production is catalyzed by phosphatidylinositol phosphate 5-kinases (PIP5K). PIP5K increased actin polymerixzation in cells. For intracellular vesicles, polymerized actin was very often associated with one side of vesicles and vesicles moved around with polymerized actin tails. Similar movement was observed in host cells infected by bacterial pathogens. At the interface between vesicle membrane and cytoplasm, increased PIP2 recruited N-WASP (Wiscott- Aldrich syndrome protein) by inositol binding region and induced conformational change. This results in the activation of its C-terminal domain to induce actin polymerization. By live cell imaging using green fluorescent protein (GFP) derivatives, we could observe dynamic intracellular vesicular movement. These results suggest that, in addition to vesicle movement on microtubules, actin polymerization is likely to contribute intracellular vesicular movement and that the levels of phosphoinositides regulate this actin based motility.

对于囊泡运输，囊泡上的分子与细胞质蛋白之间的相互作用是重要的。在本研究中，我们重点研究了囊泡膜上的磷脂酰肌醇及其磷酸化。PI的磷酸化受磷脂酰肌醇激酶和磷酸酶的调节。特别是磷脂酰肌醇(4，5)二磷酸(PIP2)对膜运输具有重要作用。PIP2的最后一步是由磷脂酰肌醇磷酸5-激酶(PIP5K)催化的。PIP5K促进细胞内肌动蛋白聚合。对于细胞内的小泡，聚合的肌动蛋白经常伴随着一侧的小泡，而小泡则伴随着聚合的肌动蛋白尾巴移动。在被细菌病原体感染的宿主细胞中也观察到了类似的运动。在囊泡膜和细胞质的交界处，增加的PIP2通过肌醇结合区募集N-WASP(Wiscott-Aldrich综合征蛋白)并诱导构象变化。这导致其C-末端结构域被激活以诱导肌动蛋白聚合。通过使用绿色荧光蛋白(GFP)衍生物的活细胞成像，我们可以观察到细胞内囊泡的动态运动。这些结果表明，除了微管上的囊泡运动外，肌动蛋白聚合可能有助于细胞内的囊泡运动，并且肌醇磷脂的水平调节这种基于肌动蛋白的运动。