Enabling Technologies Group, Sanford Research , Sioux Falls, SD, USA.
Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota , Vermillion, SD, USA.
J Cell Biol. 2024 Jul 1;223(7). doi: 10.1083/jcb.202308152. Epub 2024 Apr 29.
Nucleocytoplasmic transport (NCT), the facilitated diffusion of cargo molecules between the nucleus and cytoplasm through nuclear pore complexes (NPCs), enables numerous fundamental eukaryotic cellular processes. Ran GTPase uses cellular energy in the direct form of GTP to create a gradient across the nuclear envelope (NE) that drives the majority of NCT. We report here that changes in GTP availability resulting from altered cellular physiology modulate the rate of NCT, as monitored using synthetic and natural cargo, and the dynamics of Ran itself. Cell migration, cell spreading, and/or modulation of the cytoskeleton or its connection to the nucleus alter GTP availability and thus rates of NCT, regulating RNA export and protein synthesis. These findings support a model in which changes in cellular physiology that alter GTP availability can regulate the rate of NCT, impacting fundamental cellular processes that extensively utilize NCT.
核质转运(NCT),即通过核孔复合体(NPC)在细胞核和细胞质之间促进货物分子的扩散,使许多基本的真核细胞过程成为可能。Ran GTPase 利用细胞能量的直接形式 GTP 在核膜(NE)上产生梯度,从而驱动大多数 NCT。我们在这里报告说,改变细胞生理学导致的 GTP 可用性的变化会调节 NCT 的速率,这可以通过使用合成和天然货物以及 Ran 本身的动力学来监测。细胞迁移、细胞铺展以及/或细胞骨架或其与细胞核的连接的调节会改变 GTP 的可用性,从而改变 NCT 的速率,调节 RNA 输出和蛋白质合成。这些发现支持这样一种模型,即改变 GTP 可用性的细胞生理学变化可以调节 NCT 的速率,从而影响广泛利用 NCT 的基本细胞过程。