Mechanical force application to the nucleus regulates nucleocytoplasmic transport.
Journal
Nature cell biology
ISSN: 1476-4679
Titre abrégé: Nat Cell Biol
Pays: England
ID NLM: 100890575
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
received:
17
09
2021
accepted:
26
04
2022
pubmed:
11
6
2022
medline:
22
6
2022
entrez:
10
6
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35681009
doi: 10.1038/s41556-022-00927-7
pii: 10.1038/s41556-022-00927-7
pmc: PMC7614780
mid: EMS179322
doi:
Substances chimiques
Receptors, Cytoplasmic and Nuclear
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
896-905Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 210887
Pays : United Kingdom
Organisme : European Research Council
ID : 883739
Pays : International
Organisme : Wellcome Trust
ID : 210887/Z/18/Z
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
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