Lusk C Patrick, Morgan Kimberly J, King Megan C
Department of Cell Biology, Yale School of Medicine, New Haven, CT, USA.
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA.
Nat Cell Biol. 2025 Sep 19. doi: 10.1038/s41556-025-01768-w.
Thousands of nuclear pore complexes (NPCs) cover the nuclear surface of mammalian cells and establish selective transport conduits that biochemically segregate the nucleoplasm and cytoplasm. Although the molecular composition and structure of archetypical NPCs are well understood, distinct NPCs composed of varying nucleoporins exist in different cell types and even within individual cells. Furthermore, the integration of NPCs within mechanosensitive networks impacts their dilation state. However, whether (and how) the dilation or compositional plasticity of NPCs impacts their primary role as selective transport channels remains unclear. Based on our current understanding of NPC plasticity, we propose here that nuclear membrane tension and the resulting dilation of nuclear pores is a determinant of the compositional plasticity of NPCs, thus providing a framework to interpret how nucleoporins may influence cell fate decisions and explain the tissue-specificity of some NPC-related diseases.
数千个核孔复合体(NPC)覆盖在哺乳动物细胞的核表面,并建立起选择性运输通道,在生化层面上分隔核质和细胞质。尽管典型NPC的分子组成和结构已为人熟知,但不同细胞类型甚至单个细胞内都存在由不同核孔蛋白组成的独特NPC。此外,NPC在机械敏感网络中的整合会影响其扩张状态。然而,NPC的扩张或组成可塑性是否(以及如何)影响其作为选择性运输通道的主要功能仍不清楚。基于我们目前对NPC可塑性的理解,我们在此提出,核膜张力以及由此导致的核孔扩张是NPC组成可塑性的一个决定因素,从而提供了一个框架来解释核孔蛋白如何影响细胞命运决定,并解释一些与NPC相关疾病的组织特异性。