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

描述（由申请人提供）：控制细胞生长和大小的机制在很大程度上是未知的，代表了生物学中未解决的基本问题。我们最近发现了一个连接有丝分裂进入和膜生长的检查点。我们对这个检查点的分析提出了一个新的假设：我们提出，到达膜生长位点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，下游组件读取该信号的强度，以确定何时发生足够的生长进入有丝分裂。这一假说为细胞生物学中的两个基本问题提供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）细胞膜生长是如何与细胞周期结合的？提出的目标检验了假设的关键预测。目的1使用不同的方法，包括单细胞分析，以测试膜生长是否转化为成比例的检查点信号。目标2测试关键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。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。

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.