Mechanical control of nuclear import by Importin-7 is regulated by its dominant cargo YAP

Mechanical forces regulate multiple essential pathways in the cell. The nuclear translocation of mechanoresponsive transcriptional regulators is an essential step for mechanotransduction. However, how mechanical forces regulate the nuclear import process is not understood. Here, we identify a highly...

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Autores: Garcia-Garcia, Maria, Sánchez-Perales, Sara, Jarabo, Patricia, Calvo, Enrique, Huyton, Trevor, Fu, Liran, Ng, Sheung Chun, Sotodosos-Alonso, Laura, Vazquez, Jesus, Casas-Tinto, Sergio, Görlich, Dirk, Echarri, Asier, del Pozo, Miguel Angel
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/15634
Acceso en línea:http://hdl.handle.net/20.500.12105/15634
Access Level:acceso abierto
Palabra clave:Cell Nucleus
Mechanotransduction, Cellular
Active Transport, Cell Nucleus
Karyopherins
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spelling Mechanical control of nuclear import by Importin-7 is regulated by its dominant cargo YAPGarcia-Garcia, MariaSánchez-Perales, SaraJarabo, PatriciaCalvo, EnriqueHuyton, TrevorFu, LiranNg, Sheung ChunSotodosos-Alonso, LauraVazquez, JesusCasas-Tinto, SergioGörlich, DirkEcharri, Asierdel Pozo, Miguel AngelCell NucleusMechanotransduction, CellularActive Transport, Cell NucleusKaryopherinsMechanical forces regulate multiple essential pathways in the cell. The nuclear translocation of mechanoresponsive transcriptional regulators is an essential step for mechanotransduction. However, how mechanical forces regulate the nuclear import process is not understood. Here, we identify a highly mechanoresponsive nuclear transport receptor (NTR), Importin-7 (Imp7), that drives the nuclear import of YAP, a key regulator of mechanotransduction pathways. Unexpectedly, YAP governs the mechanoresponse of Imp7 by forming a YAP/Imp7 complex that responds to mechanical cues through the Hippo kinases MST1/2. Furthermore, YAP behaves as a dominant cargo of Imp7, restricting the Imp7 binding and the nuclear translocation of other Imp7 cargoes such as Smad3 and Erk2. Thus, the nuclear import process is an additional regulatory layer indirectly regulated by mechanical cues, which activate a preferential Imp7 cargo, YAP, which competes out other cargoes, resulting in signaling crosstalk.Nature Publishing GroupMinisterio de Ciencia e Innovación (España)Agencia Estatal de Investigación (España)Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)Comunidad de Madrid (España)Fundación La Marató TV3Fundación La CaixaAsociación Española Contra el CáncerUnión Europea. Comisión Europea. H2020Marie CurieFundación ProCNICMinisterio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)Instituto de Salud Carlos III20232023-03-1520222022-03-0420222022-03-04research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/15634reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengEuropean Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 641639open accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/156342026-06-12T12:43:37Z
dc.title.none.fl_str_mv Mechanical control of nuclear import by Importin-7 is regulated by its dominant cargo YAP
title Mechanical control of nuclear import by Importin-7 is regulated by its dominant cargo YAP
spellingShingle Mechanical control of nuclear import by Importin-7 is regulated by its dominant cargo YAP
Garcia-Garcia, Maria
Cell Nucleus
Mechanotransduction, Cellular
Active Transport, Cell Nucleus
Karyopherins
title_short Mechanical control of nuclear import by Importin-7 is regulated by its dominant cargo YAP
title_full Mechanical control of nuclear import by Importin-7 is regulated by its dominant cargo YAP
title_fullStr Mechanical control of nuclear import by Importin-7 is regulated by its dominant cargo YAP
title_full_unstemmed Mechanical control of nuclear import by Importin-7 is regulated by its dominant cargo YAP
title_sort Mechanical control of nuclear import by Importin-7 is regulated by its dominant cargo YAP
dc.creator.none.fl_str_mv Garcia-Garcia, Maria
Sánchez-Perales, Sara
Jarabo, Patricia
Calvo, Enrique
Huyton, Trevor
Fu, Liran
Ng, Sheung Chun
Sotodosos-Alonso, Laura
Vazquez, Jesus
Casas-Tinto, Sergio
Görlich, Dirk
Echarri, Asier
del Pozo, Miguel Angel
author Garcia-Garcia, Maria
author_facet Garcia-Garcia, Maria
Sánchez-Perales, Sara
Jarabo, Patricia
Calvo, Enrique
Huyton, Trevor
Fu, Liran
Ng, Sheung Chun
Sotodosos-Alonso, Laura
Vazquez, Jesus
Casas-Tinto, Sergio
Görlich, Dirk
Echarri, Asier
del Pozo, Miguel Angel
author_role author
author2 Sánchez-Perales, Sara
Jarabo, Patricia
Calvo, Enrique
Huyton, Trevor
Fu, Liran
Ng, Sheung Chun
Sotodosos-Alonso, Laura
Vazquez, Jesus
Casas-Tinto, Sergio
Görlich, Dirk
Echarri, Asier
del Pozo, Miguel Angel
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Agencia Estatal de Investigación (España)
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Comunidad de Madrid (España)
Fundación La Marató TV3
Fundación La Caixa
Asociación Española Contra el Cáncer
Unión Europea. Comisión Europea. H2020
Marie Curie
Fundación ProCNIC
Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)
Instituto de Salud Carlos III
dc.subject.none.fl_str_mv Cell Nucleus
Mechanotransduction, Cellular
Active Transport, Cell Nucleus
Karyopherins
topic Cell Nucleus
Mechanotransduction, Cellular
Active Transport, Cell Nucleus
Karyopherins
description Mechanical forces regulate multiple essential pathways in the cell. The nuclear translocation of mechanoresponsive transcriptional regulators is an essential step for mechanotransduction. However, how mechanical forces regulate the nuclear import process is not understood. Here, we identify a highly mechanoresponsive nuclear transport receptor (NTR), Importin-7 (Imp7), that drives the nuclear import of YAP, a key regulator of mechanotransduction pathways. Unexpectedly, YAP governs the mechanoresponse of Imp7 by forming a YAP/Imp7 complex that responds to mechanical cues through the Hippo kinases MST1/2. Furthermore, YAP behaves as a dominant cargo of Imp7, restricting the Imp7 binding and the nuclear translocation of other Imp7 cargoes such as Smad3 and Erk2. Thus, the nuclear import process is an additional regulatory layer indirectly regulated by mechanical cues, which activate a preferential Imp7 cargo, YAP, which competes out other cargoes, resulting in signaling crosstalk.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-03-04
2022
2022-03-04
2023
2023-03-15
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/15634
url http://hdl.handle.net/20.500.12105/15634
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv European Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 641639
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869418168347262976
score 15.811543

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