Cell cycle regulation of Golgi membrane dynamics

描述(申请人提供)：随着细胞的生长和分裂，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裂。细胞内细胞器的准确划分对于维持细胞的世代功能至关重要。有丝分裂的缺陷可能导致染色体和细胞器等重要细胞结构的错误分离和丢失。虽然对染色体和中心体的分裂过程有了更好的理解，但对膜结合细胞器的遗传却知之甚少。高尔基体是细胞功能的重要细胞器，我们对在有丝分裂过程中确保高尔基体忠实分裂的潜在机制感兴趣。在有丝分裂开始时，高度组织化的高尔基体结构在两个子细胞中形成囊泡，并在末期后期进行改革。有丝分裂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质尚不清楚，但高尔基体基质蛋白可能是候选蛋白质。在这项应用中，我们建议研究有丝分裂过程中高尔基体分裂的机制。我们的目标是确定靶向纺锤体有丝分裂高尔基体膜的成分，表征高尔基体基质蛋白GM130和GRASP65在高尔基体分割中的作用，并确定子细胞中高尔基体带重组所需的因素。这些结果将为有丝分裂的调控和高尔基体的分裂过程提供新的分子机制。 公共卫生相关性：受调控的细胞分裂对于将细胞成分传播给下一代至关重要。分割过程中的错误会导致重要器官结构和细胞器的丧失，这可能会导致癌症。我们的工作检查了在有丝分裂过程中确保高尔基体准确分裂的分子机制。

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.