| 王 萍,余自华.核孔复合体的结构及其功能[J].,2019,19(3):566-571 |
| 核孔复合体的结构及其功能 |
| The Structure and Functions of the Nuclear Pore Complexs |
| 投稿时间：2018-02-27 修订日期：2018-03-29 |
| DOI：10.13241/j.cnki.pmb.2019.03.040 |
| 中文关键词: 核孔复合体 核孔蛋白 核质转运 基因调控 有丝分裂 |
| 英文关键词: Nuclear pore complexes Nucleoporin Nucleocytoplasmic transport Gene regulation Mitosis |
| 基金项目:国家自然科学基金项目(81270766)；福建省自然科学基金项目(2015J01407) |
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| 中文摘要: |
| 摘要：核孔复合体 (Nuclear pore complexes, NPCs) 镶嵌在核膜上，是细胞核与细胞质之间的唯一通道。冷冻电子 X 射线断层扫描将环状NPCs分为三个环，分别称为胞质环、内环和核质环，胞质环上附有胞质纤丝，核质环上附有核篮。由于物种不同，NPCs由30 ~ 50多种不同的核孔蛋白 (nucleoporins, Nups) 组成，但结构和功能高度保守。根据其结构、氨基酸序列，NPCs定位和功能，Nups被分为跨膜Nups、屏障Nups、骨架Nups、胞质纤丝Nups和核篮Nups。相互间作用稳定、紧密连接的数个 Nups 可组成亚复合体。为了应对不同生理需要，NPCs处于高度动态变化中，间期和有丝分裂期均可通过组装和去组装改变核孔数量和功能。NPCs 的主要功能是调控核质转运，小分子物质可自由扩散，大分子物质则需在核转位信号和转运载体的介导下以主动运输的方式进行转运。除了核质转运这一主要功能外，Nups 还能以一个独立于转运的方式影响基因组功能。通过影响染色质结构和影响转录调控元件对靶基因的访问，Nups促进或抑制转录。在酵母，Nups介导的基因调控主要由位于NPCs中的Nups执行；在多细胞生物，不仅NPCs中的Nups，核质内游离的Nups也具有基因调控功能。此外，Nups还能通过参与形成染色质边界和形成转录记忆对基因进行调控。在增殖细胞, Nups通过与DNA修复机器相互作用，参与DNA损伤修复，保护基因组完整性。有丝分裂时，Nups协助核膜解体和中心体迁移，并通过作用于着丝粒来控制有丝分裂组件的空间定位与活性，稳定它们与微管之间的相互作用，保证纺锤体正常组装和染色体准确分离。总之，NPCs与生物分子的核质转运、基因表达和细胞周期密切相关，它的结构和功能的稳定是真核细胞生长、增殖、分化等生命活动的基本保证。 |
| 英文摘要: |
| ABSTRACT: Nuclear pore complexes (NPCs) embed the nuclear envelope (NE) and are the sole gateway between the nucleus and the cytoplasm. The donut-shaped NPC is split into three ring moieties termed cytoplasmic ring, inner ring and nucleoplasmic ring by cryo electron tomography. The three rings are sandwiched between cytoplasmic filaments and the nuclear basket. NPCs are largely conserved from yeast to human and are composed of multiple copies of approximately 30~50 different proteins termed nucleoporins (Nups). On the basis of their structure, amino acid sequence motifs, location within the NPCs and function, Nups are classified into transmembrane Nups, barrier Nups, scaffold Nups, cytoplasmic filament Nups and nuclear basket-like Nups. Nups are organized in a small set of subcomplexes, which are primarily defined by the stability of protein interactions. NPCs biogenesis occurs either during interphase or at the end of mitosis. Controlling nucleocytoplasmic transport is the main function of NPCs, which allow the free diffusion of small molecules and ions, as well as receptor-mediated transport of large macromolecules. Beyond this vital role, Nups influence genome functions in a transport-independent manner. Nups can associate with specific genes and regulate their expression by controlling the chromatin structure and accessibility of transcription factors, promoting either transcriptional activation or repression. Gene expression regulation by Nups takes place mainly at the NE-embedded Nups in yeast, while in metazoans, a subset of mobile Nups relocating in the nuclear interior perform the same gene regulatory functions. Nup-mediated gene expression regulation is also reflected by the role of Nups in the establishment of chromatin boundaries and in transcriptional memory. Additionally, in proliferative cells, Nups play a important role in genome integrity maintenance and mitotic progression. Nups facilitate the repair of a subset of persistent DNA lesions through interactions with the DNA repair machinery. In mitotic cells, Nups assist NE breakdown and centrosome migration. By ensuring the localization and function of key mitotic components, Nups promote accurate spindle assembly, mitotic progression, and faithful chromosome segregation. In conclusion, NPCs are related to nucleocytoplasmic transport, gene expression and cell cycle, which is essential to the growth, proliferation and differentiation of eukaryotic cells. |
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