Cell Cycle Regulation of Membrane Trafficking

膜运输的细胞周期调控

• 批准号: 10047988
• 负责人: Joshua Nathaniel Bembenek
• 金额: $ 28.8万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-15 至 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10047988
• 关键词: Cell; Cycle; Regulation; Membrane; Trafficking

 DESCRIPTION (provided by applicant): Understanding cell division ultimately requires a comprehensive view of the essential events that occur and the regulatory pathways that control them. While chromosome segregation is a defining feature of division, other compartments of the cell must also be carefully divided into daughter cells, and coordinated with progress through the division process. Membrane trafficking is shut down during metaphase, and resumes during late anaphase. The cell cycle signals regulating this transition are incompletely understood. Separase is a key protease that cleaves the glue holding sister chromatids together to allow chromosome separation at the onset of anaphase. Separase also has additional functions during late anaphase to promote the final events in cell division including the regulation of vesicle trafficking. This proposal describes research aimed at understanding how separase mediates vesicle trafficking events in collaboration with other closely related cell cycle regulators that have well characterized roles in chromosome segregation. Separase localizes to vesicles and is required for exocytosis. We will define the domain of separase required for vesicle localization and how vesicle localization is regulated. We will also investigate the mechanism by which separase promotes exocytosis, whether the protease activity is required, and seek new effectors that separase acts upon to trigger exocytosis. These studies will be performed using the genetically tractable C. elegans embryo supplemented by biochemical approaches with Xenopus laevis egg extracts. This work will provide new insight into how cells coordinate the essential process of chromosome segregation with other events that must occur for accurate division, which is relevant to understanding normal development and diseases such as infertility and cancer.

 描述（由申请人提供）：了解细胞分裂最终需要全面了解发生的基本事件以及控制它们的调控途径。虽然染色体分离是分裂的一个决定性特征，但细胞的其他区室也必须仔细划分。细胞周期信号在分裂过程中被关闭，并在分裂后期恢复。分离酶是一种关键的子蛋白酶，它能裂解姐妹蛋白。染色单体在一起以允许在后期开始时进行染色体分离。分离酶在后期还具有促进细胞分裂的最终事件的其他功能，包括调节囊泡运输。该提案描述了旨在了解分离酶如何协同介导囊泡事件运输的研究。与其他密切相关的细胞周期 在染色体分离中具有明确作用的调节因子。分离酶定位于囊泡，并且是胞吐作用所必需的。我们将定义囊泡定位所需的分离酶结构域以及如何调节囊泡定位，我们还将研究分离酶促进胞吐作用的机制。是否需要蛋白酶活性，并寻找分离作用以触发胞吐作用的新效应器。这些研究将使用遗传学进行。易处理的秀丽隐杆线虫胚胎辅以非洲爪蟾卵提取物的生化方法这项工作将为细胞如何协调染色体分离的基本过程与准确分裂所必须发生的其他事件提供新的见解，这与理解正常发育和疾病有关。例如不孕症和癌症。