Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, California 95064.
Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, California 95064
Genetics. 2019 Oct;213(2):517-528. doi: 10.1534/genetics.119.301012. Epub 2019 Sep 5.
Cell size is proportional to growth rate. Thus, cells growing rapidly in rich nutrients can be nearly twice the size of cells growing slowly in poor nutrients. This proportional relationship appears to hold across all orders of life, yet the underlying mechanisms are unknown. In budding yeast, most growth occurs during mitosis, and the proportional relationship between cell size and growth rate is therefore enforced primarily by modulating growth in mitosis. When growth is slow, the duration of mitosis is increased to allow more time for growth, yet the amount of growth required to complete mitosis is reduced, which leads to the birth of small daughter cells. Previous studies have found that Rts1, a member of the conserved B56 family of protein phosphatase 2A regulatory subunits, works in a TORC2 signaling network that influences cell size and growth rate. However, it was unclear whether Rts1 influences cell growth and size in mitosis. Here, we show that Rts1 is required for the proportional relationship between cell size and growth rate during mitosis. Moreover, nutrients and Rts1 influence the duration and extent of growth in mitosis via Wee1 and Pds1/securin, two conserved regulators of mitotic progression. Together, the data are consistent with a model in which global signals that set growth rate also set the critical 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.
细胞大小与生长速率成正比。因此,在丰富的营养物质中快速生长的细胞可以接近在贫瘠的营养物质中缓慢生长的细胞的两倍大小。这种比例关系似乎适用于所有生命层次,但潜在的机制尚不清楚。在出芽酵母中,大多数生长发生在有丝分裂期间,因此细胞大小与生长速率之间的比例关系主要通过调节有丝分裂期间的生长来强制实施。当生长缓慢时,有丝分裂的持续时间会延长,以允许更多的时间用于生长,但完成有丝分裂所需的生长量减少,这导致小的子细胞诞生。先前的研究发现,Rts1 是保守的 B56 家族蛋白磷酸酶 2A 调节亚基的成员,它在影响细胞大小和生长速率的 TORC2 信号网络中起作用。然而,尚不清楚 Rts1 是否会影响有丝分裂中的细胞生长和大小。在这里,我们表明 Rts1 是有丝分裂期间细胞大小与生长速率之间比例关系所必需的。此外,营养物质和 Rts1 通过 Wee1 和 Pds1/securin(两种调节有丝分裂进程的保守调节剂)影响有丝分裂期间的生长持续时间和程度。总的来说,数据与这样一个模型一致,即设定生长速率的全局信号也设定了细胞周期进程所需的临界生长量,这将为细胞大小与生长速率之间的比例关系提供一个简单的机械解释。