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Nuclear mechanics as a determinant of nuclear pore complex plasticity

Nature Cell Biology volume 27, pages 1622–1631 (2025) Cite this article

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Abstract

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.

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Fig. 1: Diagram of the nuclear envelope and nuclear transport apparatus in low and high tension states.
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Fig. 2: NPC plasticity in nup composition.
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Fig. 3: Effect of NPC diameter on NPC compositional plasticity.
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Acknowledgements

We thank members of the LusKing laboratory for inspiration. C.P.L. is supported by grants from the National Institutes of Health (NIH), including R01GM105672, R01AG090465 and R01NS122236, and M.C.K. by grants from the NIH/National Institutes of General Medical Sciences (R35GM153474) and the National Science Foundation (MCB-2420904).

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  1. Department of Cell Biology, Yale School of Medicine, New Haven, CT, USA

    C. Patrick Lusk, Kimberly J. Morgan & Megan C. King

  2. Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA

    Megan C. King

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  1. C. Patrick Lusk
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  2. Kimberly J. Morgan
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C.P.L. conceived of and wrote the manuscript with M.C.K. K.J.M. edited the manuscript and generated the figures.

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Lusk, C.P., Morgan, K.J. & King, M.C. Nuclear mechanics as a determinant of nuclear pore complex plasticity. Nat Cell Biol 27, 1622–1631 (2025). https://doi.org/10.1038/s41556-025-01768-w

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