Cell cycle regulation of Golgi membrane dynamics

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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.