European Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, Groningen, 9713 AV, The Netherlands.
Department of Cell Biology, Yale School of Medicine, CT, New Haven, USA.
FEBS Lett. 2023 Nov;597(22):2739-2749. doi: 10.1002/1873-3468.14739. Epub 2023 Sep 24.
The integrity of the nuclear envelope depends on the function of nuclear pore complexes (NPCs), transport channels that control macromolecular traffic between the nucleus and cytosol. The central importance of NPCs suggests the existence of quality control (QC) mechanisms that oversee their assembly and function. In this perspective, we emphasize the challenges associated with NPC assembly and the need for QC mechanisms that operate at various stages of an NPC's life. This includes cytosolic preassembly QC that helps enforce key nucleoporin-nucleoporin interactions and their ultimate stoichiometry in the NPC in addition to mechanisms that monitor aberrant fusion of the inner and outer nuclear membranes. Furthermore, we discuss whether and how these QC mechanisms may operate to sense faulty mature NPCs to facilitate their repair or removal. The so far uncovered mechanisms for NPC QC provide fertile ground for future research that not only benefits a better understanding of the vital role that NPCs play in cellular physiology but also how loss of NPC function and/or these QC mechanisms might be an input to aging and disease.
核膜的完整性依赖于核孔复合体（NPCs）的功能，NPC 是控制核质与细胞质之间大分子运输的通道。NPCs 的核心重要性表明存在质量控制（QC）机制来监督它们的组装和功能。在这个观点中，我们强调了 NPC 组装所面临的挑战，以及需要在 NPC 生命周期的各个阶段运作的 QC 机制。这包括细胞质预组装 QC，它有助于加强关键核孔蛋白-核孔蛋白的相互作用及其在 NPC 中的最终化学计量，以及监测核内、外膜异常融合的机制。此外，我们还讨论了这些 QC 机制是否以及如何感知有缺陷的成熟 NPC，以促进其修复或去除。迄今为止发现的 NPCQC 机制为未来的研究提供了肥沃的土壤，不仅有助于更好地理解 NPC 在细胞生理学中所起的至关重要的作用，还能了解 NPC 功能丧失和/或这些 QC 机制如何成为衰老和疾病的一个诱因。
