eNOS S-nitrosylates β-actin on Cys374 and regulates PKC-θ 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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Detalles Bibliográficos
Autores: García-Ortiz, Almudena, Martín-Cofreces, Noa B., Ibiza, Sales, Ortega, Ángel, Izquierdo-Álvarez, Alicia, Trullo, Antonio, Victor, Víctor M., Calvo, Enrique, Sot, Begoña, Martínez Ruiz, Antonio, Vázquez, Jesús, Sánchez-Madrid, Francisco, Serrador, Juan M.
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/103012
Acceso en línea:https://hdl.handle.net/20.500.14352/103012
Access Level:acceso abierto
Palabra clave:577.1
Bioquímica (Farmacia)
2302 Bioquímica
Descripción
Sumario: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-θ (PKC-θ) 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 β-actin and PKC-θ from the lamellipodium-like distal (d)- SMAC, promoting PKC-θ activation. Furthermore, eNOS-derived NO S-nitrosylated β-actinon 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-θ was corroborated by overexpression of PFN1- and actin-binding defective mutants of β-actin (C374S) and PFN1 (H119E), respectively, which reduced the coalescence of PKC-θ 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.

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