美国麻省理工学院Thomas U. Schwartz、瑞士苏黎世大学Ohad Medalia等研究人员合作发现，细胞环境可塑造核孔复合体结构。该研究于2021年10月13日在线发表于国际一流学术期刊《自然》。

研究人员表示，核孔复合体（NPC）为货物在细胞核和细胞质之间跨越核膜（NE）的运输创造了大型通道。这些多兆道尔顿的结构由大约30种不同的核蛋白组成，分布在中央运输通道周围的三个主要子结构（内环、细胞质环和核质环）。

研究人员在DLD-1细胞上使用了低温电子断层扫描，该细胞是用低温聚焦离子束铣削法制备的，从而生成了人类NPC在其原始环境中的结构模型。结果表明，与以前从纯化的NE获得的人类NPC模型相比，这个模型中的内环大大加宽；中央通道的体积增加了75%，核质和胞质环被重组。此外，NPC膜在内环复合体周围表现出不对称性。利用Nup96（细胞质环和核质环的支架核蛋白）的定向降解，研究人员观察到每个环在调节中央通道和维持膜不对称性方面的相互依赖。这些研究结果突出了NPC固有的灵活性，并表明细胞环境对NPC尺寸和结构有相当大的影响。

附：英文原文

Title: The cellular environment shapes the nuclear pore complex architecture

Author: Schuller, Anthony P., Wojtynek, Matthias, Mankus, David, Tatli, Meltem, Kronenberg-Tenga, Rafael, Regmi, Saroj G., Dip, Phat V., Lytton-Jean, Abigail K. R., Brignole, Edward J., Dasso, Mary, Weis, Karsten, Medalia, Ohad, Schwartz, Thomas U.

Issue&Volume: 2021-10-13

Abstract: Nuclear pore complexes (NPCs) create large conduits for cargo transport between the nucleus and cytoplasm across the nuclear envelope (NE)1,2,3. These multi-megadalton structures are composed of about thirty different nucleoporins that are distributed in three main substructures (the inner, cytoplasmic and nucleoplasmic rings) around the central transport channel4,5,6. Here we use cryo-electron tomography on DLD-1 cells that were prepared using cryo-focused-ion-beam milling to generate a structural model for the human NPC in its native environment. We show that—compared with previous human NPC models obtained from purified NEs—the inner ring in our model is substantially wider; the volume of the central channel is increased by 75% and the nucleoplasmic and cytoplasmic rings are reorganized. Moreover, the NPC membrane exhibits asymmetry around the inner-ring complex. Using targeted degradation of Nup96, a scaffold nucleoporin of the cytoplasmic and nucleoplasmic rings, we observe the interdependence of each ring in modulating the central channel and maintaining membrane asymmetry. Our findings highlight the inherent flexibility of the NPC and suggest that the cellular environment has a considerable influence on NPC dimensions and architecture.

DOI: 10.1038/s41586-021-03985-3

Source: https://www.nature.com/articles/s41586-021-03985-3