Endoplasmic reticulum chaperone Gp96 controls actomyosin dynamics and protects against pore-forming toxins
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10216/110344 |
Resumo: | During infection, plasma membrane (PM) blebs protect host cells against bacterial pore-forming toxins (PFTs), but were also proposed to promote pathogen dissemination. However, the details and impact of blebbing regulation during infection remained unclear. Here, we identify the endoplasmic reticulum chaperone Gp96 as a novel regulator of PFT-induced blebbing. Gp96 interacts with non-muscle myosin heavy chain IIA (NMHCIIA) and controls its activity and remodelling, which is required for appropriate coordination of bleb formation and retraction. This mechanism involves NMHCIIA-Gp96 interaction and their recruitment to PM blebs and strongly resembles retraction of uropod-like structures from polarized migrating cells, a process that also promotes NMHCIIA-Gp96 association. Consistently, Gp96 and NMHCIIA not only protect the PM integrity from listeriolysin O (LLO) during infection by Listeria monocytogenes but also affect cytoskeletal organization and cell migration. Finally, we validate the association between Gp96 and NMHCIIA in vivo and show that Gp96 is required to protect hosts from LLO-dependent killing. |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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7160 |
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Endoplasmic reticulum chaperone Gp96 controls actomyosin dynamics and protects against pore-forming toxinsActomyosin/metabolismAnimalsBacterial Proteins/metabolismBacterial Toxins/metabolismCell SurvivalHumansListeria monocytogenesMembrane Glycoproteins/metabolismMiceMolecular Chaperones/metabolismPore Forming Cytotoxic Proteins/metabolismZebrafishDuring infection, plasma membrane (PM) blebs protect host cells against bacterial pore-forming toxins (PFTs), but were also proposed to promote pathogen dissemination. However, the details and impact of blebbing regulation during infection remained unclear. Here, we identify the endoplasmic reticulum chaperone Gp96 as a novel regulator of PFT-induced blebbing. Gp96 interacts with non-muscle myosin heavy chain IIA (NMHCIIA) and controls its activity and remodelling, which is required for appropriate coordination of bleb formation and retraction. This mechanism involves NMHCIIA-Gp96 interaction and their recruitment to PM blebs and strongly resembles retraction of uropod-like structures from polarized migrating cells, a process that also promotes NMHCIIA-Gp96 association. Consistently, Gp96 and NMHCIIA not only protect the PM integrity from listeriolysin O (LLO) during infection by Listeria monocytogenes but also affect cytoskeletal organization and cell migration. Finally, we validate the association between Gp96 and NMHCIIA in vivo and show that Gp96 is required to protect hosts from LLO-dependent killing.EMBO20172017-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfapplication/pdfapplication/pdfapplication/zipapplication/zipapplication/zipapplication/zipapplication/zipapplication/zipapplication/ziphttp://hdl.handle.net/10216/110344eng1469-221X10.15252/embr.201642833Mesquita, FSBrito, CMazon, Moya MJPinheiro, JCMostowy, SCabanes, DSousa, Sinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-09-27T09:46:35Zoai:repositorio-aberto.up.pt:10216/110344Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-09-27T09:46:35Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Endoplasmic reticulum chaperone Gp96 controls actomyosin dynamics and protects against pore-forming toxins |
title |
Endoplasmic reticulum chaperone Gp96 controls actomyosin dynamics and protects against pore-forming toxins |
spellingShingle |
Endoplasmic reticulum chaperone Gp96 controls actomyosin dynamics and protects against pore-forming toxins Mesquita, FS Actomyosin/metabolism Animals Bacterial Proteins/metabolism Bacterial Toxins/metabolism Cell Survival Humans Listeria monocytogenes Membrane Glycoproteins/metabolism Mice Molecular Chaperones/metabolism Pore Forming Cytotoxic Proteins/metabolism Zebrafish |
title_short |
Endoplasmic reticulum chaperone Gp96 controls actomyosin dynamics and protects against pore-forming toxins |
title_full |
Endoplasmic reticulum chaperone Gp96 controls actomyosin dynamics and protects against pore-forming toxins |
title_fullStr |
Endoplasmic reticulum chaperone Gp96 controls actomyosin dynamics and protects against pore-forming toxins |
title_full_unstemmed |
Endoplasmic reticulum chaperone Gp96 controls actomyosin dynamics and protects against pore-forming toxins |
title_sort |
Endoplasmic reticulum chaperone Gp96 controls actomyosin dynamics and protects against pore-forming toxins |
author |
Mesquita, FS |
author_facet |
Mesquita, FS Brito, C Mazon, Moya MJ Pinheiro, JC Mostowy, S Cabanes, D Sousa, S |
author_role |
author |
author2 |
Brito, C Mazon, Moya MJ Pinheiro, JC Mostowy, S Cabanes, D Sousa, S |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Mesquita, FS Brito, C Mazon, Moya MJ Pinheiro, JC Mostowy, S Cabanes, D Sousa, S |
dc.subject.por.fl_str_mv |
Actomyosin/metabolism Animals Bacterial Proteins/metabolism Bacterial Toxins/metabolism Cell Survival Humans Listeria monocytogenes Membrane Glycoproteins/metabolism Mice Molecular Chaperones/metabolism Pore Forming Cytotoxic Proteins/metabolism Zebrafish |
topic |
Actomyosin/metabolism Animals Bacterial Proteins/metabolism Bacterial Toxins/metabolism Cell Survival Humans Listeria monocytogenes Membrane Glycoproteins/metabolism Mice Molecular Chaperones/metabolism Pore Forming Cytotoxic Proteins/metabolism Zebrafish |
description |
During infection, plasma membrane (PM) blebs protect host cells against bacterial pore-forming toxins (PFTs), but were also proposed to promote pathogen dissemination. However, the details and impact of blebbing regulation during infection remained unclear. Here, we identify the endoplasmic reticulum chaperone Gp96 as a novel regulator of PFT-induced blebbing. Gp96 interacts with non-muscle myosin heavy chain IIA (NMHCIIA) and controls its activity and remodelling, which is required for appropriate coordination of bleb formation and retraction. This mechanism involves NMHCIIA-Gp96 interaction and their recruitment to PM blebs and strongly resembles retraction of uropod-like structures from polarized migrating cells, a process that also promotes NMHCIIA-Gp96 association. Consistently, Gp96 and NMHCIIA not only protect the PM integrity from listeriolysin O (LLO) during infection by Listeria monocytogenes but also affect cytoskeletal organization and cell migration. Finally, we validate the association between Gp96 and NMHCIIA in vivo and show that Gp96 is required to protect hosts from LLO-dependent killing. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017 2017-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10216/110344 |
url |
http://hdl.handle.net/10216/110344 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1469-221X 10.15252/embr.201642833 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf application/zip application/zip application/zip application/zip application/zip application/zip application/zip |
dc.publisher.none.fl_str_mv |
EMBO |
publisher.none.fl_str_mv |
EMBO |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
mluisa.alvim@gmail.com |
_version_ |
1817548466120818688 |