Biozentrum and the Swiss Nanoscience Institute, University of Basel, Basel CH4056, Switzerland.
J Cell Sci. 2021 Apr 1;134(7). doi: 10.1242/jcs.240382. Epub 2021 Apr 13.
Macromolecular cargoes are asymmetrically partitioned in the nucleus or cytoplasm by nucleocytoplasmic transport (NCT). At the center of this activity lies the nuclear pore complex (NPC), through which soluble factors circulate to orchestrate NCT. These include cargo-carrying importin and exportin receptors from the β-karyopherin (Kapβ) family and the small GTPase Ran, which switches between guanosine triphosphate (GTP)- and guanosine diphosphate (GDP)-bound forms to regulate cargo delivery and compartmentalization. Ongoing efforts have shed considerable light on how these soluble factors traverse the NPC permeability barrier to sustain NCT. However, this does not explain how importins and exportins are partitioned in the cytoplasm and nucleus, respectively, nor how a steep RanGTP-RanGDP gradient is maintained across the nuclear envelope. In this Review, we peel away the multiple layers of control that regulate NCT and juxtapose unresolved features against known aspects of NPC function. Finally, we discuss how NPCs might function synergistically with Kapβs, cargoes and Ran to establish the asymmetry of NCT.
大分子货物通过核质转运（NCT）在细胞核或细胞质中不对称分配。在这一活动的中心是核孔复合体（NPC），可溶性因子通过 NPC 循环以协调 NCT。这些因子包括来自β核孔蛋白（Kapβ）家族的货物携带的导入蛋白和输出蛋白受体，以及小 GTPase Ran，它在鸟苷三磷酸（GTP）和鸟苷二磷酸（GDP）结合形式之间切换，以调节货物的传递和区室化。目前的研究已经阐明了这些可溶性因子如何穿过 NPC 渗透率屏障来维持 NCT。然而，这并不能解释导入蛋白和输出蛋白如何分别在细胞质和细胞核中分配，也不能解释核膜上如何维持陡峭的 RanGTP-RanGDP 梯度。在这篇综述中，我们揭示了调节 NCT 的多个控制层，并将未解决的特征与 NPC 功能的已知方面并列。最后，我们讨论了 NPC 如何与 Kapβs、货物和 Ran 协同作用，以建立 NCT 的不对称性。
