Control of cell growth and size by a novel cell cycle checkpoint mechanism

通过新型细胞周期检查点机制控制细胞生长和大小

• 批准号: 9195114
• 负责人: Douglas R. Kellogg
• 金额: $ 25.37万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA CRUZ
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-17 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9195114
• 关键词: Biochemistry; Biological; Biology; Cell Cycle; Cell Cycle Checkpoint; Cell Shape; Cell Size; Cell division; Cells; Cellular biology; Clinic; Complex; Defect; Dissociation; Elements; Ensure; Eukaryotic Cell; Excision; Genetic; Growth; Guanosine Triphosphate Phosphohydrolases; In Vitro; Link; Malignant Neoplasms; Membrane; Mitosis; Mitotic; Modeling; Monitor; Nature; Normal Cell; Output; Pathology; Phosphorylation; Protein Kinase C; Protein Phosphatase 2A Regulatory Subunit PR53; Proteins; Shapes; Signal Transduction; Site; Testing; Translating; Vesicle; Work; cancer cell; cell growth; experimental study; in vivo; in vivo imaging; inhibitor/antagonist; innovation; killings; novel; public health relevance; reconstitution; sensor; single cell analysis

DESCRIPTION (provided by applicant): The mechanisms that control cell growth and size are largely unknown and represent a fundamental unsolved problem in biology. We recently discovered a checkpoint that links mitotic entry to membrane growth. Our analysis of this checkpoint suggests a novel hypothesis: we propose that vesicles arriving at a site of membrane growth generate a checkpoint signal that is proportional to the extent of membrane growth. We further hypothesize that downstream components read the strength of this signal to determine when sufficient growth has occurred for entry into mitosis. This hypothesis suggests a simple and broadly relevant solution to two fundamental problems in cell biology: 1) How is cell size controlled? And 2) how is membrane growth integrated with the cell cycle? The proposed Aims test key predictions of the hypothesis. Aim 1 uses diverse approaches, including single cell analysis, to test whether membrane growth is translated into a proportional checkpoint signal. Aim 2 tests whether key checkpoint components translate a gradually increasing checkpoint signal into a switch-like output that triggers mitosis. Completion of the Aims will define a novel checkpoint mechanism that could control the size and shape of all eukaryotic cells.

描述(申请人提供)：控制细胞生长和大小的机制在很大程度上是未知的，是生物学中一个基本的未解决的问题。我们最近发现了一个检查点，它将有丝分裂进入与膜生长联系起来。我们对这一检查点的分析提出了一个新的假设：我们提出，到达膜生长部位的囊泡产生与膜生长程度成比例的检查点信号。我们进一步假设，下游成分读取该信号的强度，以确定何时发生了进入有丝分裂的足够生长。这一假设为细胞生物学中的两个基本问题提出了一个简单而广泛相关的解决方案：1)细胞大小是如何控制的？2)膜的生长与细胞周期是如何整合的？拟议的目标检验了这一假说的关键预测。AIM 1使用多种方法，包括单细胞分析，来测试膜生长是否转化为比例检查点信号。AIM 2测试了关键的检查点组件是否将逐渐增加的检查点信号转换为触发有丝分裂的开关样输出。这些目标的完成将定义一种新的检查点机制，可以控制所有真核细胞的大小和形状。