Control of Cell Growth and Size

我们工作的目标是发现控制细胞生长和大小的基本机制 真核细胞。我们最近的工作集中在两个关键问题上： 1.细胞如何测量和限制生长以控制细胞大小？在所有细胞中，关键的细胞周期转变 只有当足够的生长发生时，才会发生，这确保了增殖细胞保持特定的 尺码。因此，细胞必须将生长转化为触发细胞周期进程的比例信号 达到一个临界点。细胞测量生长和触发细胞周期转变的机制 一直保持着深深的神秘。我们最近的研究表明，驱动质膜的囊泡 生长将磷脂酰丝氨酸输送到生长的膜上，后者招募保守的信号蛋白 以产生与增长程度成正比的信号。此外，我们发现了一个信号 一条可以读取生长依赖信号并在到达时触发细胞周期进展的途径 一个门槛。依赖生长的信号转导机制提供了一种简单而广泛适用的解决方案来控制 细胞的生长和大小。 2.控制细胞生长和大小的信号是什么？60多年前的观察 指出控制细胞生长和大小之间的密切关系。因此，增长率与 养分利用率，细胞大小与生长速度成正比，而生长速度与细胞大小成正比。 这些关系似乎适用于生活的所有顺序，这表明它们反映了基本的 然而，根本的机制仍然难以捉摸。我们发现发出的信号 来自保守的TORC2信号网络强制营养之间的比例关系 可用性、细胞生长和细胞大小。例如，我们的工作表明，依赖于TORC2的信号 设定的生长速度还设定了细胞周期进程所需的生长阈值，这 将为细胞大小和细胞大小之间的比例关系提供一个简单的机械解释 增长率。 总之，这些新发现支持变革性假说，这些假说可以广泛地解释细胞如何 生长和大小都得到了控制。在我们未来的工作中，我们将检验由我们的 同时还进行了机制分析，以进一步绘制出显著的信令网络 来控制细胞的生长和大小。我们还将开始将我们在酵母中的发现转化为 了解脊椎动物细胞如何控制细胞生长和大小。

The goal of our work is to discover fundamental mechanisms that control cell growth and size in all eukaryotic cells. Our recent work has focused on two key questions: 1. How do cells measure and limit growth to control cell size? In all cells, key cell cycle transitions occur only when sufficient growth has occurred, which ensures that proliferating cells maintain a specific size. Thus, cells must convert growth to a proportional signal that triggers cell cycle progression when it reaches a threshold. The mechanisms by which cells measure growth and trigger cell cycle transitions have remained deeply mysterious. Our recent work suggests that vesicles that drive plasma membrane growth deliver phosphatidylserine to the growing membrane, which recruits conserved signaling proteins to generate a signal that is proportional to the extent of growth. Furthermore, we discovered a signaling pathway that could read the growth-dependent signal and trigger cell cycle progression when it reaches a threshold. Growth-dependent signaling suggests a simple and broadly applicable solution to control of cell growth and size. 2. What are the signals that control cell growth and size? Observations reaching back over 60 years point to close relationships between control of cell growth and size. Thus, growth rate is proportional to nutrient availability, cell size is proportional to growth rate, and growth rate is proportional to cell size. These relationships appear to hold across all orders of life, which suggest that they reflect fundamental principles, yet the underlying mechanisms have remained elusive. We discovered that signals arising from a conserved TORC2 signaling network enforce proportional relationships between nutrient availability, cell growth, and cell size. For example, our work suggests that TORC2-dependent signals that set growth rate also set the threshold amount of growth required for cell cycle progression, which would provide a simple mechanistic explanation for the proportional relationship between cell size and growth rate. Together, these new discoveries support transformational hypotheses that could broadly explain how cell growth and size are controlled. In our future work, we will test the key hypotheses arising from our discoveries, while also carrying out mechanistic analysis to further map the remarkable signaling networks that control cell growth and size. We will also begin translating our discoveries in yeast into an understanding of how cell growth and size are controlled in vertebrate cells.