Nuclear Pore Complex Structure and Function

The nuclear pore complex (NPC) is a large multiprotein assembly embedded within the nuclear envelope of eukaryotic cells. Comprising around thirty distinct nucleoporins arranged into structural subcomplexes, the NPC forms a cylindrical scaffold that anchors a central transport channel. Flexible phenylalanine–glycine (FG) repeat domains line the channel, establishing a selective permeability barrier that discriminates between passive diffusion of small molecules and active receptor-mediated transport of macromolecules. The NPC fulfils essential functions in gene expression, cell cycle regulation and signal transduction by mediating the bidirectional exchange of proteins, RNAs and ribonucleoprotein particles. Beyond transport, recent work has revealed roles in chromatin organisation, epigenetic transcriptional memory and cellular response to stress. NPC assembly occurs by distinct pathways in mitosis and interphase, integrating the sequential addition of scaffold and peripheral modules to accommodate nuclear growth and division. High-resolution structural studies, combined with dynamic imaging and quantitative modelling, have begun to elucidate the architecture of assembly intermediates and the flexibility of ring structures in their native environment. Dysregulation of NPC structure or transport function is implicated in human disease, including neurodegenerative disorders and cancer, underscoring its broad biological and clinical significance.

Research from Nature Portfolio

Recent studies have generated a quantitative map of human NPC assembly by tracking the stoichiometry and spatiotemporal distribution of major subcomplexes during mitotic exit and interphase. This work demonstrated that the order of central ring and filament integration is inverted between the two pathways, leading to distinct assembly intermediates and informing predictive models of NPC biogenesis. Complementary cryo-electron tomography of intact cells has revealed that the cellular milieu modulates NPC dimensions and symmetry: inner-ring complexes are wider in situ, central channels expand by approximately three-quarters of their previously measured volume, and membrane asymmetries adjust upon targeted degradation of specific scaffold nucleoporins. Together, these findings highlight both the inherent flexibility of NPC architecture and the interdependence of scaffold modules in maintaining structural integrity and transport competence.

Nuclear Pore Complex Structure and Function publication trend

The graph below shows the total number of articles in nuclear pore complex structure and function across all publications each year (not limited to Nature Index journals).

Technical terms

Nucleoporin: A protein component of the nuclear pore complex, forming scaffold and peripheral modules.

FG Repeat: Phenylalanine–glycine motifs within disordered nucleoporin domains that create a selective barrier.

Scaffold Complex: The core structural framework of the NPC, providing stability and architectural support.

Cryo-electron Tomography: A high-resolution imaging technique used to reconstruct native macromolecular assemblies in situ.

Nucleocytoplasmic Transport: The regulated movement of molecules between the nucleus and cytoplasm via transport receptors and the NPC.

References

1. A quantitative map of nuclear pore assembly reveals two distinct mechanisms. Nature (2023).
2. The cellular environment shapes the nuclear pore complex architecture. Nature (2021).
3. Nuclear pore and nucleocytoplasmic transport impairment in oxidative stress-induced neurodegeneration: relevance to molecular mechanisms in Pathogenesis of Parkinson’s and other related neurodegenerative diseases. Molecular Neurodegeneration (2024).
4. Nuclear pore assembly proceeds by an inside-out extrusion of the nuclear envelope. eLife (2016).
5. The molecular mechanism of nuclear transport revealed by atomic-scale measurements. eLife (2015).
6. A Conserved Role for Human Nup98 in Altering Chromatin Structure and Promoting Epigenetic Transcriptional Memory. PLOS Biology (2013).