Chethan Samir G, Rogers Jessie M, Vijayakumari Drisya, Williams Wendi, Gligorovski Vojislav, Rahi Sahand Jamal, Hauf Silke
Department of Biological Sciences, Virginia Tech, Blacksburg, VA 24061, USA.
Fralin Life Sciences Institute, Virginia Tech, Blacksburg, VA 24061, USA.
bioRxiv. 2025 Jun 6:2025.06.05.658100. doi: 10.1101/2025.06.05.658100.
In eukaryotes, cell division requires coordination between the nucleus and cytoplasm. Entry into cell division is driven by cyclin-dependent kinases (CDKs), which need a cyclin binding partner for their activity. In (fission yeast), the B-type cyclin Cdc13 is essential and sufficient for cell cycle progression and is strongly enriched in the nucleus. Here, we show that a fraction of Cdc13 is exported from the nucleus to the cytoplasm just prior to mitosis. This export could be critical to propagate CDK activity throughout the cell. Mutating three Cdc13 nuclear localization signals (NLSs) led to precocious enrichment of Cdc13 in the cytoplasm but did not accelerate mitotic entry, indicating that the export is not sufficient to trigger entry into mitosis. The export coincides with spindle pole body integration into the nuclear envelope and may be required to coordinate nuclear and cytoplasmic signaling required for this integration. The onset and stop of Cdc13 nuclear export are remarkably abrupt, underscoring that mitotic entry consists of several switch-like transitions over the course of minutes. Our findings add another instance to the various cyclin nuclear transport events known to occur at critical cell cycle transitions throughout eukaryotes.
在真核生物中，细胞分裂需要细胞核与细胞质之间的协调。细胞进入分裂阶段由细胞周期蛋白依赖性激酶（CDK）驱动，这些激酶需要一个细胞周期蛋白结合伴侣来发挥其活性。在裂殖酵母中，B型细胞周期蛋白Cdc13对于细胞周期进程至关重要且足够，并且在细胞核中高度富集。在这里，我们表明，一部分Cdc13在有丝分裂即将开始之前从细胞核输出到细胞质中。这种输出对于在整个细胞中传播CDK活性可能至关重要。突变三个Cdc13核定位信号（NLS）导致Cdc13在细胞质中过早富集，但并未加速有丝分裂的进入，这表明这种输出不足以触发进入有丝分裂。这种输出与纺锤极体整合到核膜中同时发生，并且可能是协调这种整合所需的核和细胞质信号传导所必需的。Cdc13核输出的开始和停止非常突然，这突出表明有丝分裂的进入在几分钟内由几个类似开关的转变组成。我们的发现为已知在整个真核生物关键细胞周期转变时发生的各种细胞周期蛋白核转运事件增添了另一个实例。
