eNOS S-nitrosylates beta-actin on Cys374 and regulates PKC-theta 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: Garcia-Ortiz, Almudena, Martin-Cofreces, Noa B., Ibiza, Sales, Ortega, Angel, Izquierdo-Alvarez, Alicia, Trullo, Antonio, Victor, Victor Manuel, Calvo, Enrique, Sot, Begona, Martinez-Ruiz, Antonio, Vazquez, Jesus, Sanchez-Madrid, Francisco, Serrador, Juan M.
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/5124
Acceso en línea:http://hdl.handle.net/20.500.12105/5124
Access Level:acceso abierto
Palabra clave:NITRIC-OXIDE SYNTHASE
T-CELL-ACTIVATION
IMMUNOLOGICAL SYNAPSE
RETROGRADE FLOW
ARP2/3 COMPLEX
PROTEIN
RECEPTOR
POLYMERIZATION
POLARIZATION
CYTOSKELETON
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-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.

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