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对发生的基本事件和控制它们的调控途径有一个全面的了解。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小心地分成子细胞，并与分裂过程的进展相协调。细胞膜运输在分裂中期被关闭，在后期恢复。调节这种转变的细胞周期信号还不完全清楚。分离酶是一种关键的蛋白酶，它在分裂后期开始时切割将姐妹染色单体连接在一起的胶水，以允许染色体分离。分离酶在细胞分裂后期还具有促进细胞分裂的最终事件的额外功能，包括调节囊泡运输。该提案描述了旨在了解分离酶如何与其他密切相关的细胞周期合作介导囊泡运输事件的研究 在染色体分离中具有良好特征作用的调节子。分离酶定位于囊泡，是胞吐作用所必需的。我们将定义分离酶的领域所需的囊泡定位和囊泡定位是如何调节的。我们也将研究分离酶促进胞吐的机制，是否需要蛋白酶活性，并寻找分离酶作用于触发胞吐的新效应物。这些研究将使用遗传上易处理的C。线虫胚胎补充生化方法与非洲爪蟾卵提取物。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必须发生的其他事件提供新的见解，这与理解正常发育和不孕症和癌症等疾病有关。