CDK control pathways integrate cell size and ploidy information to control cell division.
CDK control pathways integrate cell size and ploidy information to control cell division.
复制标题
DOI：
10.7554/elife.64592
复制
发表时间：
2021-06-11
期刊：
影响因子：
7.7
通讯作者：
Nurse P
中科院分区：
文献类型：
--
作者：
Patterson JO;Basu S;Rees P;Nurse P
维持细胞大小的稳态是整个真核生物中保守的特性。细胞大小稳态是通过细胞分裂与细胞生长的协调来实现的，并且需要限制较小的细胞进行有丝分裂和细胞分裂，同时允许较大的细胞进行有丝分裂和细胞分裂。细胞周期蛋白-CDK是有丝分裂的基本驱动力，因此最终确保大小稳态。在这里，我们解剖的CDK活性在体内的决定因素，探讨细胞大小的信息是如何处理的细胞周期网络在裂变酵母。我们开发了一个高通量的单细胞测定系统的CDK活性在体内，并显示抑制性酪氨酸磷酸化的CDK编码细胞大小的信息，与磷酸酶PP 2A帮助设置一个大小阈值分裂。CDK抑制性磷酸化与PP 2A协同作用以防止较小细胞中的有丝分裂。最后，我们发现，二倍体细胞的大小相当的单倍体细胞表现出较低的CDK活性，在响应相等的细胞周期蛋白-CDK酶浓度，这表明CDK活性降低DNA水平的增加。因此，细胞周期蛋白-CDK水平与细胞大小、CDK抑制性磷酸化、PP 2A和CDK活性的DNA依赖性抑制的比例关系都告知细胞大小的细胞周期网络，从而有助于细胞大小的稳态。
Maintenance of cell size homeostasis is a property that is conserved throughout eukaryotes. Cell size homeostasis is brought about by the co-ordination of cell division with cell growth and requires restriction of smaller cells from undergoing mitosis and cell division, whilst allowing larger cells to do so. Cyclin-CDK is the fundamental driver of mitosis and therefore ultimately ensures size homeostasis. Here we dissect determinants of CDK activity in vivo to investigate how cell size information is processed by the cell cycle network in fission yeast. We develop a high-throughput single-cell assay system of CDK activity in vivo and show that inhibitory tyrosine phosphorylation of CDK encodes cell size information, with the phosphatase PP2A aiding to set a size threshold for division. CDK inhibitory phosphorylation works synergistically with PP2A to prevent mitosis in smaller cells. Finally, we find that diploid cells of equivalent size to haploid cells exhibit lower CDK activity in response to equal cyclin-CDK enzyme concentrations, suggesting that CDK activity is reduced by increased DNA levels. Therefore, scaling of cyclin-CDK levels with cell size, CDK inhibitory phosphorylation, PP2A, and DNA-dependent inhibition of CDK activity, all inform the cell cycle network of cell size, thus contributing to cell size homeostasis.