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: 8026349
• 负责人: JOACHIM SEEMANN
• 金额: $ 31.7万
• 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/8026349
• 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; 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. PUBLIC HEALTH RELEVANCE: Regulated cell division is essential to propagate cellular components to the next generation. Mistakes in the partitioning process leads to the loss of vitals structures and organelles, which may lead to cancer. Our work examines the molecular mechanisms that ensure the accurate division of the Golgi apparatus during mitosis.

描述（由申请人提供）：当细胞生长和分裂时，细胞器必须在间期复制，并在有丝分裂时在两个子细胞之间分裂。胞内细胞器的准确分配是维持细胞功能的关键。有丝分裂缺陷可导致错误分离和重要的细胞结构，如染色体和细胞器的损失。虽然对染色体和中心体的分配过程有了更好的了解，但对膜结合细胞器的遗传知之甚少。高尔基体是细胞功能的重要细胞器，我们对有丝分裂过程中确保高尔基体忠实分配的潜在机制很感兴趣。在有丝分裂开始时，高度组织化的高尔基结构在两个子细胞的末期形成囊泡并重组。有丝分裂的高尔基膜聚集在纺锤体极点和星状微管周围，表明高尔基分裂是由有丝分裂纺锤体组织的。连接高尔基体和纺锤体的蛋白是未知的，但高尔基基质蛋白可能是候选蛋白。在这个应用程序中，我们建议研究在有丝分裂过程中组织高尔基体分裂的机制。我们的目标是确定将有丝分裂的高尔基膜靶向纺锤体的成分，表征高尔基基质蛋白GM130和GRASP65在高尔基分割中的作用，并确定子细胞中高尔基带重组所需的因素。该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见解。