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（由适用提供）：了解细胞分裂最终需要对发生的基本事件以及控制它们的监管途径的全面看法。虽然染色体分离是分裂的定义特征，但细胞的其他隔室也必须小心地分为子细胞，并通过分裂过程进行了协调。中期期间关闭膜贩运，并在后期后期恢复。计算此转变的细胞周期信号尚不完全理解。分离酶是一种关键蛋白，将胶水夹在一起的胶水将姊妹染色质裂解在一起，以便在后期开始时染色体分离。分离酶在后期后期还具有其他功能，可促进细胞分裂的最终事件，包括调节囊泡运输。该建议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表征作用的调节剂。分离酶定位于蔬菜，是胞吐作用所必需的。我们将定义蔬菜定位所需的分离酶的结构域以及如何调节蔬菜定位。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，并寻求分离酶作用的新作用来触发胞吐作用。这些研究将使用一般可牵引的秀丽隐杆线虫胚胎进行，该秀丽隐杆线虫的胚胎是用爪蟾laevis鸡蛋提取物补充的。这项工作将提供新的见解，了解细胞如何将染色体隔离的基本过程与其他必须发生的事件进行精确分裂的事件，这与理解正常发育和疾病（例如不育和癌症）有关。