Mechanical force application to the nucleus regulates nucleocytoplasmic transport

Ion Andreu*, Ignasi Granero-Moya, Nimesh R. Chahare, Kessem Clein, Marc Molina-Jordán, Amy E.M. Beedle, Alberto Elosegui-Artola, Juan F. Abenza, Leone Rossetti, Xavier Trepat, Barak Raveh, Pere Roca-Cusachs*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Mechanical force controls fundamental cellular processes in health and disease, and increasing evidence shows that the nucleus both experiences and senses applied forces. Such forces can lead to the nuclear translocation of proteins, but whether force controls nucleocytoplasmic transport, and how, remains unknown. Here we show that nuclear forces differentially control passive and facilitated nucleocytoplasmic transport, setting the rules for the mechanosensitivity of shuttling proteins. We demonstrate that nuclear force increases permeability across nuclear pore complexes, with a dependence on molecular weight that is stronger for passive than for facilitated diffusion. Owing to this differential effect, force leads to the translocation of cargoes into or out of the nucleus within a given range of molecular weight and affinity for nuclear transport receptors. Further, we show that the mechanosensitivity of several transcriptional regulators can be both explained by this mechanism and engineered exogenously by introducing appropriate nuclear localization signals. Our work unveils a mechanism of mechanically induced signalling, probably operating in parallel with others, with potential applicability across signalling pathways.

Original languageAmerican English
Pages (from-to)896-905
Number of pages10
JournalNature Cell Biology
Volume24
Issue number6
DOIs
StatePublished - Jun 2022

Bibliographical note

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Limited.

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