Caveolae couple mechanical stress to integrin recycling and activation

Autores
Lolo, Fidel Nicolás; Pavón, Dácil M.; Grande García, Araceli; Elósegui Artola, Alberto; Segatori, Valeria Inés; Sánchez Perales, Sara; Trepat, Xavier; Roca Cusachs, Pere; Del Pozo, Miguel A.
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Cells are subjected to multiple mechanical inputs throughout their lives. Their ability to detect these environmental cues is called mechanosensing, a process in which integrins play an important role. During cellular mechanosensing, plasma membrane (PM) tension is adjusted to mechanical stress through the buffering action of caveolae; however, little is known about the role of caveolae in early integrin mechanosensing regulation. Here, we show that Cav1KO fibroblasts increase adhesion to FN-coated beads when pulled with magnetic tweezers, as compared to wild type fibroblasts. This phenotype is Rho-independent and mainly derived from increased active β1-integrin content on the surface of Cav1KO fibroblasts. FRAP analysis and endocytosis/recycling assays revealed that active β1-integrin is mostly endocytosed through the CLIC/GEEC pathway and is more rapidly recycled to the PM in Cav1KO fibroblasts, in a Rab4 and PM tension-dependent manner. Moreover, the threshold for PM tension-driven β1-integrin activation is lower in Cav1KO MEFs than in wild type MEFs, through a mechanism dependent on talin activity. Our findings suggest that caveolae couple mechanical stress to integrin cycling and activation, thereby regulating the early steps of the cellular mechanosensing response.
Fil: Lolo, Fidel Nicolás. Centro Nacional de Investigaciones Cardiovasculares; España
Fil: Pavón, Dácil M.. Centro Nacional de Investigaciones Cardiovasculares; España
Fil: Grande García, Araceli. Centro Nacional de Investigaciones Cardiovasculares; España
Fil: Elósegui Artola, Alberto. Instituto de Bioingeniería de Cataluña; España
Fil: Segatori, Valeria Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sánchez Perales, Sara. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Trepat, Xavier. Instituto de Bioingeniería de Cataluña; España
Fil: Roca Cusachs, Pere. Instituto de Bioingeniería de Cataluña; España
Fil: Del Pozo, Miguel A.. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
CAVEOLAE
INTEGRIN
MECHANICAL STRESS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/201035
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/201035
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Caveolae couple mechanical stress to integrin recycling and activationLolo, Fidel NicolásPavón, Dácil M.Grande García, AraceliElósegui Artola, AlbertoSegatori, Valeria InésSánchez Perales, SaraTrepat, XavierRoca Cusachs, PereDel Pozo, Miguel A.CAVEOLAEINTEGRINMECHANICAL STRESShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Cells are subjected to multiple mechanical inputs throughout their lives. Their ability to detect these environmental cues is called mechanosensing, a process in which integrins play an important role. During cellular mechanosensing, plasma membrane (PM) tension is adjusted to mechanical stress through the buffering action of caveolae; however, little is known about the role of caveolae in early integrin mechanosensing regulation. Here, we show that Cav1KO fibroblasts increase adhesion to FN-coated beads when pulled with magnetic tweezers, as compared to wild type fibroblasts. This phenotype is Rho-independent and mainly derived from increased active β1-integrin content on the surface of Cav1KO fibroblasts. FRAP analysis and endocytosis/recycling assays revealed that active β1-integrin is mostly endocytosed through the CLIC/GEEC pathway and is more rapidly recycled to the PM in Cav1KO fibroblasts, in a Rab4 and PM tension-dependent manner. Moreover, the threshold for PM tension-driven β1-integrin activation is lower in Cav1KO MEFs than in wild type MEFs, through a mechanism dependent on talin activity. Our findings suggest that caveolae couple mechanical stress to integrin cycling and activation, thereby regulating the early steps of the cellular mechanosensing response.Fil: Lolo, Fidel Nicolás. Centro Nacional de Investigaciones Cardiovasculares; EspañaFil: Pavón, Dácil M.. Centro Nacional de Investigaciones Cardiovasculares; EspañaFil: Grande García, Araceli. Centro Nacional de Investigaciones Cardiovasculares; EspañaFil: Elósegui Artola, Alberto. Instituto de Bioingeniería de Cataluña; EspañaFil: Segatori, Valeria Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sánchez Perales, Sara. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Trepat, Xavier. Instituto de Bioingeniería de Cataluña; EspañaFil: Roca Cusachs, Pere. Instituto de Bioingeniería de Cataluña; EspañaFil: Del Pozo, Miguel A.. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaeLife Sciences Publications2022-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/201035Lolo, Fidel Nicolás; Pavón, Dácil M.; Grande García, Araceli; Elósegui Artola, Alberto; Segatori, Valeria Inés; et al.; Caveolae couple mechanical stress to integrin recycling and activation; eLife Sciences Publications; eLife; 11; 10-2022; 1-262050-084XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://elifesciences.org/articles/82348info:eu-repo/semantics/altIdentifier/doi/10.7554/eLife.82348info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:46:28Zoai:ri.conicet.gov.ar:11336/201035instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:46:29.018CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Caveolae couple mechanical stress to integrin recycling and activation
title Caveolae couple mechanical stress to integrin recycling and activation
spellingShingle Caveolae couple mechanical stress to integrin recycling and activation
Lolo, Fidel Nicolás
CAVEOLAE
INTEGRIN
MECHANICAL STRESS
title_short Caveolae couple mechanical stress to integrin recycling and activation
title_full Caveolae couple mechanical stress to integrin recycling and activation
title_fullStr Caveolae couple mechanical stress to integrin recycling and activation
title_full_unstemmed Caveolae couple mechanical stress to integrin recycling and activation
title_sort Caveolae couple mechanical stress to integrin recycling and activation
dc.creator.none.fl_str_mv Lolo, Fidel Nicolás
Pavón, Dácil M.
Grande García, Araceli
Elósegui Artola, Alberto
Segatori, Valeria Inés
Sánchez Perales, Sara
Trepat, Xavier
Roca Cusachs, Pere
Del Pozo, Miguel A.
author Lolo, Fidel Nicolás
author_facet Lolo, Fidel Nicolás
Pavón, Dácil M.
Grande García, Araceli
Elósegui Artola, Alberto
Segatori, Valeria Inés
Sánchez Perales, Sara
Trepat, Xavier
Roca Cusachs, Pere
Del Pozo, Miguel A.
author_role author
author2 Pavón, Dácil M.
Grande García, Araceli
Elósegui Artola, Alberto
Segatori, Valeria Inés
Sánchez Perales, Sara
Trepat, Xavier
Roca Cusachs, Pere
Del Pozo, Miguel A.
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CAVEOLAE
INTEGRIN
MECHANICAL STRESS
topic CAVEOLAE
INTEGRIN
MECHANICAL STRESS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Cells are subjected to multiple mechanical inputs throughout their lives. Their ability to detect these environmental cues is called mechanosensing, a process in which integrins play an important role. During cellular mechanosensing, plasma membrane (PM) tension is adjusted to mechanical stress through the buffering action of caveolae; however, little is known about the role of caveolae in early integrin mechanosensing regulation. Here, we show that Cav1KO fibroblasts increase adhesion to FN-coated beads when pulled with magnetic tweezers, as compared to wild type fibroblasts. This phenotype is Rho-independent and mainly derived from increased active β1-integrin content on the surface of Cav1KO fibroblasts. FRAP analysis and endocytosis/recycling assays revealed that active β1-integrin is mostly endocytosed through the CLIC/GEEC pathway and is more rapidly recycled to the PM in Cav1KO fibroblasts, in a Rab4 and PM tension-dependent manner. Moreover, the threshold for PM tension-driven β1-integrin activation is lower in Cav1KO MEFs than in wild type MEFs, through a mechanism dependent on talin activity. Our findings suggest that caveolae couple mechanical stress to integrin cycling and activation, thereby regulating the early steps of the cellular mechanosensing response.
Fil: Lolo, Fidel Nicolás. Centro Nacional de Investigaciones Cardiovasculares; España
Fil: Pavón, Dácil M.. Centro Nacional de Investigaciones Cardiovasculares; España
Fil: Grande García, Araceli. Centro Nacional de Investigaciones Cardiovasculares; España
Fil: Elósegui Artola, Alberto. Instituto de Bioingeniería de Cataluña; España
Fil: Segatori, Valeria Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sánchez Perales, Sara. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Trepat, Xavier. Instituto de Bioingeniería de Cataluña; España
Fil: Roca Cusachs, Pere. Instituto de Bioingeniería de Cataluña; España
Fil: Del Pozo, Miguel A.. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Cells are subjected to multiple mechanical inputs throughout their lives. Their ability to detect these environmental cues is called mechanosensing, a process in which integrins play an important role. During cellular mechanosensing, plasma membrane (PM) tension is adjusted to mechanical stress through the buffering action of caveolae; however, little is known about the role of caveolae in early integrin mechanosensing regulation. Here, we show that Cav1KO fibroblasts increase adhesion to FN-coated beads when pulled with magnetic tweezers, as compared to wild type fibroblasts. This phenotype is Rho-independent and mainly derived from increased active β1-integrin content on the surface of Cav1KO fibroblasts. FRAP analysis and endocytosis/recycling assays revealed that active β1-integrin is mostly endocytosed through the CLIC/GEEC pathway and is more rapidly recycled to the PM in Cav1KO fibroblasts, in a Rab4 and PM tension-dependent manner. Moreover, the threshold for PM tension-driven β1-integrin activation is lower in Cav1KO MEFs than in wild type MEFs, through a mechanism dependent on talin activity. Our findings suggest that caveolae couple mechanical stress to integrin cycling and activation, thereby regulating the early steps of the cellular mechanosensing response.
publishDate 2022
dc.date.none.fl_str_mv 2022-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/201035
Lolo, Fidel Nicolás; Pavón, Dácil M.; Grande García, Araceli; Elósegui Artola, Alberto; Segatori, Valeria Inés; et al.; Caveolae couple mechanical stress to integrin recycling and activation; eLife Sciences Publications; eLife; 11; 10-2022; 1-26
2050-084X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/201035
identifier_str_mv Lolo, Fidel Nicolás; Pavón, Dácil M.; Grande García, Araceli; Elósegui Artola, Alberto; Segatori, Valeria Inés; et al.; Caveolae couple mechanical stress to integrin recycling and activation; eLife Sciences Publications; eLife; 11; 10-2022; 1-26
2050-084X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://elifesciences.org/articles/82348
info:eu-repo/semantics/altIdentifier/doi/10.7554/eLife.82348
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv eLife Sciences Publications
publisher.none.fl_str_mv eLife Sciences Publications
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842268797512187904
score 13.13397

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