2026-07-22T00:21:33Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/51242024-09-27T08:17:01Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605col_20.500.12105_19607
Repisalud
author
Garcia-Ortiz, Almudena
author
Martin-Cofreces, Noa B.
author
Ibiza, Sales
author
Ortega, Angel
author
Izquierdo-Alvarez, Alicia
author
Trullo, Antonio
author
Victor, Victor Manuel
author
Calvo, Enrique
author
Sot, Begona
author
Martinez-Ruiz, Antonio
author
Vazquez, Jesus
author
Sanchez-Madrid, Francisco
author
Serrador, Juan M.
funder
Instituto de Salud Carlos III
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Ministerio de Economía, Industria y Competitividad (España)
funder
Unión Europea. Comisión Europea
2017-10-20T10:23:13Z
2017-10-20T10:23:13Z
2017
PLoS Biol. 2017; 15(4):e2000653
10.1371/journal.pbio.2000653
1545-7885
Plos Biology
28394935
http://hdl.handle.net/20.500.12105/5124
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.
eng
NITRIC-OXIDE SYNTHASE
T-CELL-ACTIVATION
IMMUNOLOGICAL SYNAPSE
RETROGRADE FLOW
ARP2/3 COMPLEX
PROTEIN
RECEPTOR
POLYMERIZATION
POLARIZATION
CYTOSKELETON
eNOS S-nitrosylates beta-actin on Cys374 and regulates PKC-theta at the immune synapse by impairing actin binding to profilin-1
journal article
URL
https://repisalud.isciii.es/bitstreams/591c0936-b10d-442e-9706-45600d47d8b3/download
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b694654a6c29821a9fff616374ec09ee
4009350
application/pdf
eNOSS-nitrosylatesβ-actinOnCys374_2017
URL
https://repisalud.isciii.es/bitstreams/0b473433-589c-4faa-b656-bbc918307436/download
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2a5e38fc7ebe87a38c8b166c263c0458
125657
text/plain
eNOSS-nitrosylatesβ-actinOnCys374_2017.txt
URL
https://repisalud.isciii.es/bitstreams/214f5d74-e34c-41fe-9549-a50c939ac540/download
File
MD5
2a5e38fc7ebe87a38c8b166c263c0458
125657
text/plain
eNOSS-nitrosylatesβ-actinOnCys374_2017.txt