TorsinA folding and N-linked glycosylation are sensitive to redox homeostasis

Autores
Honer, Jonas; Niemeyer, Katie M.; Fercher, Christian; Diez Tissera, Ana Laura; Jaberolansar, Noushin; Jafrani, Yohaann M.A.; Zhou, Chun; Caramelo, Julio Javier; Shewan, Annette M.; Schulz, Benjamin L.; Brodsky, Jeffrey L.; Zacchi, Lucia Florencia
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The Endoplasmic Reticulum (ER) is responsible for the folding and post-translational modification of secretory proteins, as well as for triaging misfolded proteins. During folding, there is a complex yet only partially understood interplay between disulfide bond formation, which is an enzyme catalyzed event in the oxidizing environment of the ER, along with other post-translational modifications (PTMs) and chaperone-supported protein folding. Here, we used the glycoprotein torsinA as a model substrate to explore the impact of ER redox homeostasis on PTMs and protein biogenesis. TorsinA is a AAA+ ATPase with unusual oligomeric properties and controversial functions. The deletion of a C-terminal glutamic acid residue (∆E) is associated with the development of Early-Onset Torsion Dystonia, a severe movement disorder. TorsinA differs from other AAA+ ATPases since it is an ER resident, and as a result of its entry into the ER torsinA contains two N-linked glycans and at least one disulfide bond. The role of these PTMs on torsinA biogenesis and function and the identity of the enzymes that catalyze them are poorly defined. Using a yeast torsinA expression system, we demonstrate that a specific protein disulfide isomerase, Pdi1, affects the folding and N-linked glycosylation of torsinA and torsinA∆E in a redox-dependent manner, suggesting that the acquisition of early torsinA folding intermediates is sensitive to perturbed interactions between Cys residues and the quality control machinery. We also highlight the role of specific Cys residues during torsinA biogenesis and demonstrate that torsinA∆E is more sensitive than torsinA when these Cys residues are mutated.
Fil: Honer, Jonas. University of Pittsburgh; Estados Unidos
Fil: Niemeyer, Katie M.. University of Pittsburgh; Estados Unidos
Fil: Fercher, Christian. The University of Queensland; Australia
Fil: Diez Tissera, Ana Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Jaberolansar, Noushin. The University of Queensland; Australia
Fil: Jafrani, Yohaann M.A.. The University of Queensland; Australia
Fil: Zhou, Chun. The University of Queensland; Australia
Fil: Caramelo, Julio Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Shewan, Annette M.. The University of Queensland; Australia
Fil: Schulz, Benjamin L.. The University of Queensland; Australia
Fil: Brodsky, Jeffrey L.. University of Pittsburgh; Estados Unidos
Fil: Zacchi, Lucia Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. University of Pittsburgh; Estados Unidos. The University of Queensland; Australia
Materia
DYSTONIA
N-LINKED GLYCOSYLATION
POST-TRANSLATIONAL MODIFICATIONS
PROTEIN DISULFIDE ISOMERASE
PROTEIN FOLDING
TORSINA
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/167147
Acceder
id CONICETDig_2b0b6ef5596aabee1731c11be7af158e
oai_identifier_str oai:ri.conicet.gov.ar:11336/167147
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling TorsinA folding and N-linked glycosylation are sensitive to redox homeostasisHoner, JonasNiemeyer, Katie M.Fercher, ChristianDiez Tissera, Ana LauraJaberolansar, NoushinJafrani, Yohaann M.A.Zhou, ChunCaramelo, Julio JavierShewan, Annette M.Schulz, Benjamin L.Brodsky, Jeffrey L.Zacchi, Lucia FlorenciaDYSTONIAN-LINKED GLYCOSYLATIONPOST-TRANSLATIONAL MODIFICATIONSPROTEIN DISULFIDE ISOMERASEPROTEIN FOLDINGTORSINAhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The Endoplasmic Reticulum (ER) is responsible for the folding and post-translational modification of secretory proteins, as well as for triaging misfolded proteins. During folding, there is a complex yet only partially understood interplay between disulfide bond formation, which is an enzyme catalyzed event in the oxidizing environment of the ER, along with other post-translational modifications (PTMs) and chaperone-supported protein folding. Here, we used the glycoprotein torsinA as a model substrate to explore the impact of ER redox homeostasis on PTMs and protein biogenesis. TorsinA is a AAA+ ATPase with unusual oligomeric properties and controversial functions. The deletion of a C-terminal glutamic acid residue (∆E) is associated with the development of Early-Onset Torsion Dystonia, a severe movement disorder. TorsinA differs from other AAA+ ATPases since it is an ER resident, and as a result of its entry into the ER torsinA contains two N-linked glycans and at least one disulfide bond. The role of these PTMs on torsinA biogenesis and function and the identity of the enzymes that catalyze them are poorly defined. Using a yeast torsinA expression system, we demonstrate that a specific protein disulfide isomerase, Pdi1, affects the folding and N-linked glycosylation of torsinA and torsinA∆E in a redox-dependent manner, suggesting that the acquisition of early torsinA folding intermediates is sensitive to perturbed interactions between Cys residues and the quality control machinery. We also highlight the role of specific Cys residues during torsinA biogenesis and demonstrate that torsinA∆E is more sensitive than torsinA when these Cys residues are mutated.Fil: Honer, Jonas. University of Pittsburgh; Estados UnidosFil: Niemeyer, Katie M.. University of Pittsburgh; Estados UnidosFil: Fercher, Christian. The University of Queensland; AustraliaFil: Diez Tissera, Ana Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Jaberolansar, Noushin. The University of Queensland; AustraliaFil: Jafrani, Yohaann M.A.. The University of Queensland; AustraliaFil: Zhou, Chun. The University of Queensland; AustraliaFil: Caramelo, Julio Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Shewan, Annette M.. The University of Queensland; AustraliaFil: Schulz, Benjamin L.. The University of Queensland; AustraliaFil: Brodsky, Jeffrey L.. University of Pittsburgh; Estados UnidosFil: Zacchi, Lucia Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. University of Pittsburgh; Estados Unidos. The University of Queensland; AustraliaElsevier Science2021-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/167147Honer, Jonas; Niemeyer, Katie M.; Fercher, Christian; Diez Tissera, Ana Laura; Jaberolansar, Noushin; et al.; TorsinA folding and N-linked glycosylation are sensitive to redox homeostasis; Elsevier Science; Biochimica et Biophysica Acta-Molecular Cell Research; 1868; 9; 8-2021; 1-130167-48891879-2596CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbamcr.2021.119073info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0167488921001270info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:56:22Zoai:ri.conicet.gov.ar:11336/167147instacron: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 09:56:23.795CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv TorsinA folding and N-linked glycosylation are sensitive to redox homeostasis
title TorsinA folding and N-linked glycosylation are sensitive to redox homeostasis
spellingShingle TorsinA folding and N-linked glycosylation are sensitive to redox homeostasis
Honer, Jonas
DYSTONIA
N-LINKED GLYCOSYLATION
POST-TRANSLATIONAL MODIFICATIONS
PROTEIN DISULFIDE ISOMERASE
PROTEIN FOLDING
TORSINA
title_short TorsinA folding and N-linked glycosylation are sensitive to redox homeostasis
title_full TorsinA folding and N-linked glycosylation are sensitive to redox homeostasis
title_fullStr TorsinA folding and N-linked glycosylation are sensitive to redox homeostasis
title_full_unstemmed TorsinA folding and N-linked glycosylation are sensitive to redox homeostasis
title_sort TorsinA folding and N-linked glycosylation are sensitive to redox homeostasis
dc.creator.none.fl_str_mv Honer, Jonas
Niemeyer, Katie M.
Fercher, Christian
Diez Tissera, Ana Laura
Jaberolansar, Noushin
Jafrani, Yohaann M.A.
Zhou, Chun
Caramelo, Julio Javier
Shewan, Annette M.
Schulz, Benjamin L.
Brodsky, Jeffrey L.
Zacchi, Lucia Florencia
author Honer, Jonas
author_facet Honer, Jonas
Niemeyer, Katie M.
Fercher, Christian
Diez Tissera, Ana Laura
Jaberolansar, Noushin
Jafrani, Yohaann M.A.
Zhou, Chun
Caramelo, Julio Javier
Shewan, Annette M.
Schulz, Benjamin L.
Brodsky, Jeffrey L.
Zacchi, Lucia Florencia
author_role author
author2 Niemeyer, Katie M.
Fercher, Christian
Diez Tissera, Ana Laura
Jaberolansar, Noushin
Jafrani, Yohaann M.A.
Zhou, Chun
Caramelo, Julio Javier
Shewan, Annette M.
Schulz, Benjamin L.
Brodsky, Jeffrey L.
Zacchi, Lucia Florencia
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv DYSTONIA
N-LINKED GLYCOSYLATION
POST-TRANSLATIONAL MODIFICATIONS
PROTEIN DISULFIDE ISOMERASE
PROTEIN FOLDING
TORSINA
topic DYSTONIA
N-LINKED GLYCOSYLATION
POST-TRANSLATIONAL MODIFICATIONS
PROTEIN DISULFIDE ISOMERASE
PROTEIN FOLDING
TORSINA
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The Endoplasmic Reticulum (ER) is responsible for the folding and post-translational modification of secretory proteins, as well as for triaging misfolded proteins. During folding, there is a complex yet only partially understood interplay between disulfide bond formation, which is an enzyme catalyzed event in the oxidizing environment of the ER, along with other post-translational modifications (PTMs) and chaperone-supported protein folding. Here, we used the glycoprotein torsinA as a model substrate to explore the impact of ER redox homeostasis on PTMs and protein biogenesis. TorsinA is a AAA+ ATPase with unusual oligomeric properties and controversial functions. The deletion of a C-terminal glutamic acid residue (∆E) is associated with the development of Early-Onset Torsion Dystonia, a severe movement disorder. TorsinA differs from other AAA+ ATPases since it is an ER resident, and as a result of its entry into the ER torsinA contains two N-linked glycans and at least one disulfide bond. The role of these PTMs on torsinA biogenesis and function and the identity of the enzymes that catalyze them are poorly defined. Using a yeast torsinA expression system, we demonstrate that a specific protein disulfide isomerase, Pdi1, affects the folding and N-linked glycosylation of torsinA and torsinA∆E in a redox-dependent manner, suggesting that the acquisition of early torsinA folding intermediates is sensitive to perturbed interactions between Cys residues and the quality control machinery. We also highlight the role of specific Cys residues during torsinA biogenesis and demonstrate that torsinA∆E is more sensitive than torsinA when these Cys residues are mutated.
Fil: Honer, Jonas. University of Pittsburgh; Estados Unidos
Fil: Niemeyer, Katie M.. University of Pittsburgh; Estados Unidos
Fil: Fercher, Christian. The University of Queensland; Australia
Fil: Diez Tissera, Ana Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Jaberolansar, Noushin. The University of Queensland; Australia
Fil: Jafrani, Yohaann M.A.. The University of Queensland; Australia
Fil: Zhou, Chun. The University of Queensland; Australia
Fil: Caramelo, Julio Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Shewan, Annette M.. The University of Queensland; Australia
Fil: Schulz, Benjamin L.. The University of Queensland; Australia
Fil: Brodsky, Jeffrey L.. University of Pittsburgh; Estados Unidos
Fil: Zacchi, Lucia Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. University of Pittsburgh; Estados Unidos. The University of Queensland; Australia
description The Endoplasmic Reticulum (ER) is responsible for the folding and post-translational modification of secretory proteins, as well as for triaging misfolded proteins. During folding, there is a complex yet only partially understood interplay between disulfide bond formation, which is an enzyme catalyzed event in the oxidizing environment of the ER, along with other post-translational modifications (PTMs) and chaperone-supported protein folding. Here, we used the glycoprotein torsinA as a model substrate to explore the impact of ER redox homeostasis on PTMs and protein biogenesis. TorsinA is a AAA+ ATPase with unusual oligomeric properties and controversial functions. The deletion of a C-terminal glutamic acid residue (∆E) is associated with the development of Early-Onset Torsion Dystonia, a severe movement disorder. TorsinA differs from other AAA+ ATPases since it is an ER resident, and as a result of its entry into the ER torsinA contains two N-linked glycans and at least one disulfide bond. The role of these PTMs on torsinA biogenesis and function and the identity of the enzymes that catalyze them are poorly defined. Using a yeast torsinA expression system, we demonstrate that a specific protein disulfide isomerase, Pdi1, affects the folding and N-linked glycosylation of torsinA and torsinA∆E in a redox-dependent manner, suggesting that the acquisition of early torsinA folding intermediates is sensitive to perturbed interactions between Cys residues and the quality control machinery. We also highlight the role of specific Cys residues during torsinA biogenesis and demonstrate that torsinA∆E is more sensitive than torsinA when these Cys residues are mutated.
publishDate 2021
dc.date.none.fl_str_mv 2021-08
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/11336/167147
Honer, Jonas; Niemeyer, Katie M.; Fercher, Christian; Diez Tissera, Ana Laura; Jaberolansar, Noushin; et al.; TorsinA folding and N-linked glycosylation are sensitive to redox homeostasis; Elsevier Science; Biochimica et Biophysica Acta-Molecular Cell Research; 1868; 9; 8-2021; 1-13
0167-4889
1879-2596
CONICET Digital
CONICET
url http://hdl.handle.net/11336/167147
identifier_str_mv Honer, Jonas; Niemeyer, Katie M.; Fercher, Christian; Diez Tissera, Ana Laura; Jaberolansar, Noushin; et al.; TorsinA folding and N-linked glycosylation are sensitive to redox homeostasis; Elsevier Science; Biochimica et Biophysica Acta-Molecular Cell Research; 1868; 9; 8-2021; 1-13
0167-4889
1879-2596
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbamcr.2021.119073
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0167488921001270
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
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
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score 13.13397

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