Graduate School of Frontier Biosciences, Osaka University, Suita 565-0871, Japan.
Curr Biol. 2010 Nov 9;20(21):1919-25. doi: 10.1016/j.cub.2010.09.070. Epub 2010 Oct 21.
Asymmetric localization of Ran regulators (RanGAP1 and RanGEF/RCC1) produces a gradient of RanGTP across the nuclear envelope. In higher eukaryotes, the nuclear envelope breaks down as the cell enters mitosis (designated "open" mitosis). This nuclear envelope breakdown (NEBD) leads to collapse of the RanGTP gradient and the diffusion of nuclear and cytoplasmic macromolecules in the cell, resulting in irreversible progression of the cell cycle. On the other hand, in many fungi, chromosome segregation takes place without NEBD (designated "closed" mitosis). Here we report that in the fission yeast Schizosaccharomyces pombe, despite the nuclear envelope and the nuclear pore complex remaining intact throughout both the meiotic and mitotic cell cycles, nuclear proteins diffuse into the cytoplasm transiently for a few minutes at the onset of anaphase of meiosis II. We also found that nuclear protein diffusion into the cytoplasm occurred coincidently with nuclear localization of Rna1, an S. pombe RanGAP1 homolog that is usually localized in the cytoplasm. These results suggest that nuclear localization of RanGAP1 and depression of RanGTP activity in the nucleus may be mechanistically tied to meiosis-specific diffusion of nuclear proteins into the cytoplasm. This nucleocytoplasmic shuffling of RanGAP1 and nuclear proteins represents virtual breakdown of the nuclear envelope.
Ran 调节因子（RanGAP1 和 RanGEF/RCC1）的不对称定位在核膜上产生 RanGTP 的浓度梯度。在高等真核生物中，随着细胞进入有丝分裂（称为“开放”有丝分裂），核膜会破裂。这种核膜破裂（NEBD）导致 RanGTP 梯度的崩溃和核内和细胞质大分子在细胞中的扩散，从而导致细胞周期的不可逆进展。另一方面，在许多真菌中，染色体分离发生在没有 NEBD 的情况下（称为“封闭”有丝分裂）。在这里，我们报告说，在裂殖酵母 Schizosaccharomyces pombe 中，尽管核膜和核孔复合物在整个减数分裂和有丝分裂细胞周期中保持完整，但核蛋白在减数分裂 II 后期开始时会短暂地扩散到细胞质中几分钟。我们还发现，核蛋白向细胞质的扩散与 Rna1 的核定位同时发生，Rna1 是 S. pombe RanGAP1 同源物，通常位于细胞质中。这些结果表明，RanGAP1 的核定位和 RanGTP 活性在核内的抑制可能与减数分裂特异性核蛋白向细胞质的扩散在机制上有关。RanGAP1 和核蛋白的这种核质穿梭代表了核膜的虚拟破裂。
