Human T-cell receptor triggering requires inactivation of Lim kinase-1 by Slingshot-1 phosphatase.

Humans Lim Kinases / metabolism Receptors, Antigen, T-Cell / metabolism Phosphoprotein Phosphatases / metabolism Actins / metabolism Lymphocyte Activation Jurkat Cells T-Lymphocytes / metabolism Signal Transduction Immunological Synapses / metabolism

Journal

Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179

Informations de publication

Date de publication:
30 Jul 2024
Historique:
received: 12 02 2024
accepted: 19 07 2024
medline: 31 7 2024
pubmed: 31 7 2024
entrez: 30 7 2024
Statut: epublish

Résumé

Actin dynamics control early T-cell receptor (TCR) signalling during T-cell activation. However, the precise regulation of initial actin rearrangements is not completely understood. Here, we have investigated the regulatory role of the phosphatase Slingshot-1 (SSH1) in this process. Our data show that SSH1 rapidly polarises to nascent cognate synaptic contacts and later relocalises to peripheral F-actin networks organised at the mature immunological synapse. Knockdown of SSH1 expression by CRISPR/Cas9-mediated genome editing or small interfering RNA reveal a regulatory role for SSH1 in CD3ε conformational change, allowing Nck binding and proper downstream signalling and immunological synapse organisation. TCR triggering induces SSH1-mediated activation of actin dynamics through a mechanism mediated by Limk-1 inactivation. These data suggest that during early TCR activation, SSH1 is required for rapid F-actin rearrangements that mediate initial conformational changes of the TCR, integrin organisation and proximal signalling events for proper synapse organisation. Therefore, the SSH1 and Limk-1 axis is a key regulatory element for full T cell activation.

Identifiants

DOI: 10.1038/s42003-024-06605-8 PMID: 39080357
pubmed: 39080357
doi: 10.1038/s42003-024-06605-8
pii: 10.1038/s42003-024-06605-8
doi:

Substances chimiques

Lim Kinases EC 2.7.11.1
Receptors, Antigen, T-Cell 0
SSH1 protein, human EC 3.1.3.16
Phosphoprotein Phosphatases EC 3.1.3.16
LIMK1 protein, human EC 2.7.11.1
Actins 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

918

Subventions

Organisme : Comunidad de Madrid
ID : Y2018/BIO-5207_SINERGY_CAM
Organisme : Ministry of Economy and Competitiveness | Agencia Estatal de Investigación (Spanish Agencia Estatal de Investigación)
ID : PID2020-115444GB-I00

Informations de copyright

© 2024. The Author(s).

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Auteurs

Álvaro Gómez-Morón (Á)

Department of Immunology, Ophthalmology and ENT, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain.
12 de Octubre Health Research Institute (imas12), 28040, Madrid, Spain.
Immunology Service, Instituto de Investigación Sanitaria del Hospital Universitario La Princesa, IIS-Princesa, UAM, 28006, Madrid, Spain.

Sergio Alegre-Gómez (S)

Department of Immunology, Ophthalmology and ENT, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain.
12 de Octubre Health Research Institute (imas12), 28040, Madrid, Spain.

Rocio Ramirez-Muñoz (R)

Department of Immunology, Ophthalmology and ENT, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain.
12 de Octubre Health Research Institute (imas12), 28040, Madrid, Spain.

Alicia Hernaiz-Esteban (A)

Department of Immunology, Ophthalmology and ENT, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain.
12 de Octubre Health Research Institute (imas12), 28040, Madrid, Spain.

Carlos Carrasco-Padilla (C)

Department of Immunology, Ophthalmology and ENT, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain.
12 de Octubre Health Research Institute (imas12), 28040, Madrid, Spain.

Camila Scagnetti (C)

Immunology Service, Instituto de Investigación Sanitaria del Hospital Universitario La Princesa, IIS-Princesa, UAM, 28006, Madrid, Spain.
Videomicroscopy Unit, Instituto de Investigación Sanitaria del Hospital Universitario La Princesa, IIS-Princesa, UAM, 28006, Madrid, Spain.

Óscar Aguilar-Sopeña (Ó)

Department of Immunology, Ophthalmology and ENT, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain.
12 de Octubre Health Research Institute (imas12), 28040, Madrid, Spain.

Marta García-Gil (M)

Department of Immunology, Ophthalmology and ENT, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain.
12 de Octubre Health Research Institute (imas12), 28040, Madrid, Spain.

Aldo Borroto (A)

Centro de Biología Molecular Severo Ochoa, Campus de Cantoblanco, 28049, Madrid, Spain.

Raul Torres-Ruiz (R)

Molecular Cytogenetics and Genome Editing Unit, Human Cancer Genetics Program, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029, Madrid, Spain.
Division of Hematopoietic Innovative Therapies, Biomedical Innovation Unit, Centro de Investigaciones Energéticas, Medioambientales y Tecnologicas (CIEMAT); Advanced Therapies Unit, Instituto de Investigacion Sanitaria Fundacion Jiménez Díaz; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28040, Madrid, Spain.
Advanced Therapies Unit, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD, UAM), 28040, Madrid, Spain.

Sandra Rodriguez-Perales (S)

Molecular Cytogenetics and Genome Editing Unit, Human Cancer Genetics Program, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029, Madrid, Spain.
ORCID: 0000-0001-7221-3636

Francisco Sánchez-Madrid (F)

Immunology Service, Instituto de Investigación Sanitaria del Hospital Universitario La Princesa, IIS-Princesa, UAM, 28006, Madrid, Spain.
Area of Vascular Pathophysiology, Laboratory of Intercellular Communication, Fundación Centro Nacional de Investigaciones Cardiovasculares-Carlos III, 28029, Madrid, Spain.
CIBER de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.

Noa Beatriz Martín-Cófreces (NB)

Immunology Service, Instituto de Investigación Sanitaria del Hospital Universitario La Princesa, IIS-Princesa, UAM, 28006, Madrid, Spain. noa.martin@salud.madrid.org.
Videomicroscopy Unit, Instituto de Investigación Sanitaria del Hospital Universitario La Princesa, IIS-Princesa, UAM, 28006, Madrid, Spain. noa.martin@salud.madrid.org.
Area of Vascular Pathophysiology, Laboratory of Intercellular Communication, Fundación Centro Nacional de Investigaciones Cardiovasculares-Carlos III, 28029, Madrid, Spain. noa.martin@salud.madrid.org.
CIBER de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain. noa.martin@salud.madrid.org.
ORCID: 0000-0003-0439-8979

Pedro Roda-Navarro (P)

Department of Immunology, Ophthalmology and ENT, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain. proda@ucm.es.
12 de Octubre Health Research Institute (imas12), 28040, Madrid, Spain. proda@ucm.es.
ORCID: 0000-0003-3799-8823

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Human T-cell receptor triggering requires...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines à domaine LIM › Lim Kinases › Human T-cell receptor triggering requires...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs aux antigènes › Récepteurs aux antigènes des cellules T › Human T-cell receptor triggering requires...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Phosphoprotein Phosphatases › Human T-cell receptor triggering requires...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du cytosquelette › Protéines des microfilaments › Actines › Human T-cell receptor triggering requires...
questionsmedicales.fr › Phénomènes du système immunitaire › Activation des lymphocytes › Human T-cell receptor triggering requires...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Cellules Jurkat › Human T-cell receptor triggering requires...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Human T-cell receptor triggering requires...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Human T-cell receptor triggering requires...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Synapses immunologiques › Human T-cell receptor triggering requires...