Cell cycle regulation of Golgi membrane dynamics

高尔基体膜动力学的细胞周期调节

• 批准号: 8598095
• 负责人: JOACHIM SEEMANN
• 金额: $ 31.8万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8598095
• 关键词: Binding; Biochemical; Biological; Biological Assay; Brefeldin A; Cell Cycle Regulation; Cell division; Cell physiology; Cells; Cellular Structures; Centrosome; Chromosomes; Cytokinesis; Defect; Endoplasmic Reticulum; Ensure; Enzymes; Fractionation; Generations; Goals; Golgi Apparatus; Golgi Targeting; Growth; Importins; Interphase; Laboratories; Lead; Life; Link; Malignant Neoplasms; Membrane; Methods; Microinjections; Microscopy; Microtubules; Mitosis; Mitotic; Mitotic spindle; Molecular; Organelles; Pathway interactions; Phosphorylation; Process; Proteins; Regulation; Reporter; Reporting; Resolution; Role; Structure; Time; Vesicle; Work; cellular imaging; daughter cell; domain mapping; in vitro Assay; insight; interest; link protein; next generation; novel; novel strategies; overexpression; public health relevance; segregation; telophase

DESCRIPTION (provided by applicant): As cells grow and divide, organelles have to be duplicated in interphase and partitioned between the two daughter cells during mitosis. Accurate partitioning of intracellular organelles is crucial to sustain cellular functions over generations. Defects in mitosis can lead to the missegregation and loss of vital cellular structures such as chromosomes and organelles. While the partitioning processes are better understood for chromosomes and centrosomes, far less is known about the inheritance of membrane bound organelles. The Golgi is an essential organelle for cellular function and we are interested in the underlying mechanisms that ensure the faithful partitioning of the Golgi during mitosis. At the onset of mitosis, the highly organized Golgi structure vesiculates and reforms later in telophase in the two daughter cells. The mitotic Golgi membranes accumulate around the spindle poles and astral microtubules, suggesting that Golgi partitioning is organized by the mitotic spindle. The proteins that link Golgi to the spindle are unknown, but Golgi matrix proteins may be candidate proteins. In this application we propose to investigate the mechanisms that organize the division of the Golgi apparatus during mitosis. Our aims are to identify the components that target mitotic Golgi membranes to the spindle, characterize the role of the Golgi matrix proteins GM130 and GRASP65 in Golgi partitioning and to determine the factors required for reformation of a Golgi ribbon in the daughter cells. The results will provide new molecular mechanistic insights into the regulation of mitosis and the division process of the Golgi.

描述（由申请人提供）：随着细胞生长和分裂，细胞器必须在间期复制，并在有丝分裂期间在两个子细胞之间分配。细胞内细胞器的精确分配对于维持细胞功能的世代至关重要。有丝分裂的缺陷会导致重要细胞结构如染色体和细胞器的错误分离和丢失。虽然分配过程是更好地了解染色体和中心体，少得多的是已知的膜结合细胞器的遗传。高尔基体是细胞功能的基本细胞器，我们感兴趣的是在有丝分裂过程中，确保忠实的高尔基体分区的潜在机制。在有丝分裂开始时，高度组织化的高尔基体结构囊泡化，并在后期在两个子细胞中进行重组。有丝分裂的高尔基体膜聚集在纺锤体极和星形微管周围，表明高尔基体的分配是由有丝分裂的纺锤体组织的。连接高尔基体和纺锤体的蛋白质是未知的，但高尔基体基质蛋白可能是候选蛋白质。在这个应用程序中，我们建议调查的机制，组织分裂的高尔基体在有丝分裂。我们的目的是确定有丝分裂高尔基膜的纺锤体的组件，高尔基体基质蛋白GM130和GRASP65在高尔基体分区的作用，并确定所需的因素，在子细胞中的高尔基体丝带的改造。这些结果将为有丝分裂和高尔基体分裂过程的调控提供新的分子机制。