A spatial gradient coordinates cell size and mitotic entry in fission yeast
A spatial gradient coordinates cell size and mitotic entry in fission yeast
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DOI：
10.1038/nature08074
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发表时间：
2009-06-11
期刊：
影响因子：
64.8
通讯作者：
Nurse, Paul
中科院分区：
文献类型：
--
作者：
Moseley, James B.;Mayeux, Adeline;Nurse, Paul
许多真核细胞类型都经历了由无处不在细胞周期蛋白依赖性激酶CDK1控制的大小依赖性细胞周期转变（参考文献1-4）。控制CDK1活性的蛋白质得到了很好的描述，但它们与监测细胞尺寸的机制的联系仍然难以捉摸。在裂变酵母菌型酸酯pombe中，由于CDK1的调节活性，细胞在定义且可重复的大小上进入有丝分裂并分裂（参考2、3）。在这里，我们表明，位于细胞末端的细胞极性蛋白激酶POM1调节有助于控制有丝分裂进入的信号网络。该网络位于相间细胞中间的皮质节点，这些节点包含CDK1抑制剂WEE1，WEE1抑制性激酶CDR1（也称为NIM1）和CDR2，以及Anillin样蛋白MID1。 CDR2建立了其他蛋白质在节点中的层次定位，并从POM1接收负调节信号。 POM1形成了从细胞末端延伸至细胞中间的极梯度，并充当剂量依赖性有丝分裂进入的抑制剂，通过CDR2途径工作。随着细胞的拉长，POM1水平在细胞中间降低，导致有丝分裂进入。我们提出，POM1极梯度和内侧皮质淋巴结会产生有关细胞大小的信息，并通过通过POM1，CDR2，CDR1和WEE1调节CDK1来与有丝分裂进入。
Many eukaryotic cell types undergo size-dependent cell cycle transitions controlled by the ubiquitous cyclin-dependent kinase Cdk1 (refs 1-4). The proteins that control Cdk1 activity are well described but their links with mechanisms monitoring cell size remain elusive. In the fission yeast Schizosaccharomyces pombe, cells enter mitosis and divide at a defined and reproducible size owing to the regulated activity of Cdk1 (refs 2, 3). Here we show that the cell polarity protein kinase Pom1, which localizes to cell ends(5), regulates a signalling network that contributes to the control of mitotic entry. This network is located at cortical nodes in the middle of interphase cells, and these nodes contain the Cdk1 inhibitor Wee1, the Wee1-inhibitory kinases Cdr1 (also known as Nim1) and Cdr2, and the anillin-like protein Mid1. Cdr2 establishes the hierarchical localization of other proteins in the nodes, and receives negative regulatory signals from Pom1. Pom1 forms a polar gradient extending from the cell ends towards the cell middle and acts as a dose-dependent inhibitor of mitotic entry, working through the Cdr2 pathway. As cells elongate, Pom1 levels decrease at the cell middle, leading to mitotic entry. We propose that the Pom1 polar gradient and the medial cortical nodes generate information about cell size and coordinate this with mitotic entry by regulating Cdk1 through Pom1, Cdr2, Cdr1 and Wee1.