Spatial regulation of exocytosis

胞吐作用的空间调节

基本信息

批准号：
7344840
负责人：
WEI GUO
金额：
$ 28.75万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-09-05 至 2009-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7344840
关键词：
Active Sites Affect Affinity Chromatography Biochemical Biological Assay Biological Process Caenorhabditis elegans Cell Communication Cell Cycle Progression Cell Cycle Stage Cell division Cell membrane Cell secretion Cells Complex Condition Cytosol Deletion Mutagenesis Docking Eukaryotic Cell Exocytosis Family Fractionation Furuncles GTP Binding GTP-Binding Proteins Gene Deletion Genes Genetic Genetic Screening Goals Guanosine Triphosphate Phosphohydrolases Homologous Gene Immunoprecipitation In Vitro Kidney Diseases Lateral Lead Localized Mediating Membrane Molecular Molecular Conformation Monomeric GTP-Binding Proteins Morphogenesis Multiprotein Complexes Nature Neoplasm Metastasis Numbers Pathway interactions Process Proteins Regulation of Exocytosis Research Research Personnel Rest Role Route Saccharomyces cerevisiae Saccharomycetales Secretory Vesicles Signal Pathway Signal Transduction Site Testing Vesicle Yeasts cancer cell cell growth computerized data processing member mutant nervous system disorder polarized cell programs protein function protein protein interaction research study rho rho GTP-Binding Proteins

项目摘要

DESCRIPTION (provided by applicant): My goal is to understand how the Rho family of small GTPases control polarized exocytosis through the secretory vesicle docking complex, the exocyst. Spatial regulation of exocytosis is fundamental to many biological processes such as cell growth, polarity establishment, and cell-cell communication. Abnormalities in these fundamental processes may lead to pathological conditions such as cancer cell metastasis, neurological disorders, and kidney diseases. Polarized exocytosis involves directional transport, docking, and fusion of secretory vesicles with specific domains of the plasma membrane. An evolutionarily conserved multi-protein complex, the "exocyst" specifically localizes to sites of active secretion and serves as the basic vesicle docking machinery at the plasma membrane. Our recent studies using the budding yeast Saccharomyces cerevisiae revealed that Rho 1, a member of the Rho family of small GTP-binding proteins, interacts with the exocyst and regulate the localization of the exocyst during each stage of the cell cycle. Here we propose to identify and characterize the proteins involved in the signal transduction from Rho 1 to the exocyst using a combination of genetic, cytological, and biochemical approaches. Furthermore, we will test our hypothesis that Rho 1 interacts with the exocyst components to facilitate their polarized assembly at the plasma membrane. Finally, we will investigate how Rho 1 coordinates exocytosis with morphogenesis and polarized cell growth. These studies are crucial to our understanding of the molecular network controlling polarized secretion in eukaryotic cells.

描述（由申请人提供）：我的目标是了解小gtpases的Rho家族如何通过分泌囊泡对胞外囊肿的分泌囊泡综合体控制两极分化的胞吐作用。胞吐作用的空间调节是许多生物学过程的基础，例如细胞生长，极性建立和细胞 - 细胞通信。这些基本过程中的异常可能导致病理状况，例如癌细胞转移，神经系统疾病和肾脏疾病。极化胞吐作用涉及与质膜特定结构域的分泌囊泡的定向转运，对接和融合。一种进化保守的多蛋白质复合物，“外囊”专门定位于活性分泌位点，并用作质膜的基本囊泡对接机械。我们最近使用酿酒酵母的萌芽酵母菌糖疗法的研究表明，Rho 1是小型GTP结合蛋白的Rho家族的成员，与外囊肿相互作用，并调节细胞周期每个阶段外囊肿的定位。在这里，我们建议使用遗传，细胞学和生化方法的组合来识别和表征与从Rho 1转导向外囊肿的信号转导相关的蛋白质。此外，我们将检验我们的假设，即Rho 1与外囊肿成分相互作用，以促进其在质膜上的极化组件。最后，我们将研究Rho 1如何坐坐胞胞胞菌与形态发生和极化细胞生长。这些研究对于我们对控制真核细胞极化分泌的分子网络的理解至关重要。