ACAP4蛋白介导膜泡运输的结构基础与调节机制

项目名称： ACAP4蛋白介导膜泡运输的结构基础与调节机制

项目编号： No.31271518

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 王峰松

作者单位： 安徽医科大学

项目金额： 85万元

中文摘要： 膜泡运输是细胞内最基本的生命活动过程之一，它调节和维系着许多重要的生命现象，包括细胞内信号转导、细胞器的形成、细胞迁移和极化形成等，其过程往往伴随着膜的动态性变化和细胞骨架的重排等，并受到多种蛋白的严格监控。ACAP4是由我们鉴定出来的一个新的ARF6激活蛋白，它含有BAR、PH、GAP等多结构域，初步研究结果表明ACAP4可能在膜泡运输、骨架重排、细胞迁移等多个方面具有功能，但其时空动力学特征、分子调控规律、信号转导分子机理及所涉及的生化途径等还有待进一步阐述。我们拟采用先进的生物光子学、细胞生物学、实验动物学等方法和手段，对ACAP4的结构进行精确解析并对ACAP4及其结合蛋白在膜泡运输过程中的功能和磷酸化调控机理进行深入研究,这有助于加深我们对膜泡运输本质和分子调控机制的认识，提高我们对膜泡运输相关疾病发生机制的了解，为解析涉及ACAP4功能异常疾病的纠正提供理论依据及解决方案。

中文关键词： ACAP4；结构域；膜泡运输；骨架重排；磷酸化

英文摘要： Intracellular membrane trafficking, which always accompanies with cell membrane dynamics and cytoskeleton reorganization, plays a key role in regulating diverse cellular processes, such as intracellular signal transduction, organelle structure formation, cell migration and cell polarity.It also is a complicated process,which is regulated and controlled by many proteins.Our previous research identified a novel ARF6 GAP protein, which contains BAR domain, pleckstrin homology (PH) domain and conserved GAP domain.Our data show that ACAP4 plays a key role in membrane traffick and the actin-based cytoskeletal remodeling.However,our understanding to the regulation and the molecular mechanism of ACAP4 function is very limited.Thus,we propose to combine bio-photonics,biochemistry,cell biology,biophysics and experimental animal model to distect the membrane-sculpting properties of the BAR and PH domain contributes to the regulatory role of ACAP4 in the membrane-cytoskeleton dynamics and membrane trafficking.We also want to find more ACAP4 interacted proteins and demonstrate the signaling pathway,related key molecular network and the role of phosphorylation of ACAP4's special sites.Finally,our proposed study will not only reveal the fundamental molecular mechanism of membrane trafficking but also lay a solid foundation fo

英文关键词： ACAP4；domain；membrane trafficking；cytoskeletal remodeling；phosphorylation