eNOS S-nitrosylates ß-actin on Cys374 and regulates PKC-? at the immune synapse by impairing actin binding to profilin-1

The actin cytoskeleton coordinates the organization of signaling microclusters at the immune synapse (IS); however, the mechanisms involved remain poorly understood. We show here that nitric oxide (NO) generated by endothelial nitric oxide synthase (eNOS) controls the coalescence of protein kinase C...

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Autores: García-Ortiz A, Martín-Cofreces NB, Ibiza S, Ortega Á, Izquierdo-Álvarez A, Trullo A, Victor VM, Calvo E, Sot B, Martínez-Ruiz A, Vázquez J, Sánchez-Madrid F, Serrador JM
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
Repositorio:r-FISABIO. Repositorio Institucional de Producción Científica
OAI Identifier:oai:fisabio.fundanetsuite.com:p1949
Acceso en línea:https://fisabio.portalinvestigacion.com/publicaciones/1949
Access Level:acceso abierto
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spelling eNOS S-nitrosylates ß-actin on Cys374 and regulates PKC-? at the immune synapse by impairing actin binding to profilin-1García-Ortiz AMartín-Cofreces NBIbiza SOrtega ÁIzquierdo-Álvarez ATrullo AVictor VMCalvo ESot BMartínez-Ruiz AVázquez JSánchez-Madrid FSerrador JMThe actin cytoskeleton coordinates the organization of signaling microclusters at the immune synapse (IS); however, the mechanisms involved remain poorly understood. We show here that nitric oxide (NO) generated by endothelial nitric oxide synthase (eNOS) controls the coalescence of protein kinase C-theta (PKC-theta) at the central supramolecular activation cluster (c-SMAC) of the IS. eNOS translocated with the Golgi to the IS and partially colocalized with F-actin around the c-SMAC. This resulted in reduced actin polymerization and centripetal retrograde flow of beta-actin and PKC-theta from the lamellipodium-like distal (d)-SMAC, promoting PKC-theta. activation. Furthermore, eNOS-derived NO S-nitrosylated beta-actin on Cys374 and impaired actin binding to profilin-1 (PFN1), as confirmed with the transnitrosylating agent S-nitroso-L-cysteine (Cys-NO). The importance of NO and the formation of PFN1-actin complexes on the regulation of PKC-theta. was corroborated by overexpression of PFN1- and actin-binding defective mutants of beta-actin (C374S) and PFN1 (H119E), respectively, which reduced the coalescence of PKC-theta. at the c-SMAC. These findings unveil a novel NO-dependent mechanism by which the actin cytoskeleton controls the organization and activation of signaling microclusters at the IS.PUBLIC LIBRARY SCIENCE2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fisabio.portalinvestigacion.com/publicaciones/1949PLOS BIOLOGYISSN: 15449173ISSNe: 15457885reponame:r-FISABIO. Repositorio Institucional de Producción Científicainstname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)Inglésinfo:eu-repo/semantics/openAccessoai:fisabio.fundanetsuite.com:p19492026-06-11T12:45:17Z
dc.title.none.fl_str_mv eNOS S-nitrosylates ß-actin on Cys374 and regulates PKC-? at the immune synapse by impairing actin binding to profilin-1
title eNOS S-nitrosylates ß-actin on Cys374 and regulates PKC-? at the immune synapse by impairing actin binding to profilin-1
spellingShingle eNOS S-nitrosylates ß-actin on Cys374 and regulates PKC-? at the immune synapse by impairing actin binding to profilin-1
García-Ortiz A
title_short eNOS S-nitrosylates ß-actin on Cys374 and regulates PKC-? at the immune synapse by impairing actin binding to profilin-1
title_full eNOS S-nitrosylates ß-actin on Cys374 and regulates PKC-? at the immune synapse by impairing actin binding to profilin-1
title_fullStr eNOS S-nitrosylates ß-actin on Cys374 and regulates PKC-? at the immune synapse by impairing actin binding to profilin-1
title_full_unstemmed eNOS S-nitrosylates ß-actin on Cys374 and regulates PKC-? at the immune synapse by impairing actin binding to profilin-1
title_sort eNOS S-nitrosylates ß-actin on Cys374 and regulates PKC-? at the immune synapse by impairing actin binding to profilin-1
dc.creator.none.fl_str_mv García-Ortiz A
Martín-Cofreces NB
Ibiza S
Ortega Á
Izquierdo-Álvarez A
Trullo A
Victor VM
Calvo E
Sot B
Martínez-Ruiz A
Vázquez J
Sánchez-Madrid F
Serrador JM
author García-Ortiz A
author_facet García-Ortiz A
Martín-Cofreces NB
Ibiza S
Ortega Á
Izquierdo-Álvarez A
Trullo A
Victor VM
Calvo E
Sot B
Martínez-Ruiz A
Vázquez J
Sánchez-Madrid F
Serrador JM
author_role author
author2 Martín-Cofreces NB
Ibiza S
Ortega Á
Izquierdo-Álvarez A
Trullo A
Victor VM
Calvo E
Sot B
Martínez-Ruiz A
Vázquez J
Sánchez-Madrid F
Serrador JM
author2_role author
author
author
author
author
author
author
author
author
author
author
author
description The actin cytoskeleton coordinates the organization of signaling microclusters at the immune synapse (IS); however, the mechanisms involved remain poorly understood. We show here that nitric oxide (NO) generated by endothelial nitric oxide synthase (eNOS) controls the coalescence of protein kinase C-theta (PKC-theta) at the central supramolecular activation cluster (c-SMAC) of the IS. eNOS translocated with the Golgi to the IS and partially colocalized with F-actin around the c-SMAC. This resulted in reduced actin polymerization and centripetal retrograde flow of beta-actin and PKC-theta from the lamellipodium-like distal (d)-SMAC, promoting PKC-theta. activation. Furthermore, eNOS-derived NO S-nitrosylated beta-actin on Cys374 and impaired actin binding to profilin-1 (PFN1), as confirmed with the transnitrosylating agent S-nitroso-L-cysteine (Cys-NO). The importance of NO and the formation of PFN1-actin complexes on the regulation of PKC-theta. was corroborated by overexpression of PFN1- and actin-binding defective mutants of beta-actin (C374S) and PFN1 (H119E), respectively, which reduced the coalescence of PKC-theta. at the c-SMAC. These findings unveil a novel NO-dependent mechanism by which the actin cytoskeleton controls the organization and activation of signaling microclusters at the IS.
publishDate 2017
dc.date.none.fl_str_mv 2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fisabio.portalinvestigacion.com/publicaciones/1949
url https://fisabio.portalinvestigacion.com/publicaciones/1949
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv PUBLIC LIBRARY SCIENCE
publisher.none.fl_str_mv PUBLIC LIBRARY SCIENCE
dc.source.none.fl_str_mv PLOS BIOLOGY
ISSN: 15449173
ISSNe: 15457885
reponame:r-FISABIO. Repositorio Institucional de Producción Científica
instname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
instname_str Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
reponame_str r-FISABIO. Repositorio Institucional de Producción Científica
collection r-FISABIO. Repositorio Institucional de Producción Científica
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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