The chaperonin CCT controls T cell receptor-driven 3D configuration of centrioles.


Journal

Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440

Informations de publication

Date de publication:
12 2020
Historique:
received: 13 03 2020
accepted: 19 10 2020
entrez: 3 12 2020
pubmed: 4 12 2020
medline: 15 4 2022
Statut: epublish

Résumé

T lymphocyte activation requires the formation of immune synapses (IS) with antigen-presenting cells. The dynamics of membrane receptors, signaling scaffolds, microfilaments, and microtubules at the IS determine the potency of T cell activation and subsequent immune response. Here, we show that the cytosolic chaperonin CCT (chaperonin-containing TCP1) controls the changes in reciprocal orientation of the centrioles and polarization of the tubulin dynamics induced by T cell receptor in T lymphocytes forming an IS. CCT also controls the mitochondrial ultrastructure and the metabolic status of T cells, regulating the de novo synthesis of tubulin as well as posttranslational modifications (poly-glutamylation, acetylation, Δ1 and Δ2) of αβ-tubulin heterodimers, fine-tuning tubulin dynamics. These changes ultimately determine the function and organization of the centrioles, as shown by three-dimensional reconstruction of resting and stimulated primary T cells using cryo-soft x-ray tomography. Through this mechanism, CCT governs T cell activation and polarity.

Identifiants

pubmed: 33268369
pii: 6/49/eabb7242
doi: 10.1126/sciadv.abb7242
pmc: PMC7821906
pii:
doi:

Substances chimiques

Receptors, Antigen, T-Cell 0
Tubulin 0
Chaperonin Containing TCP-1 EC 3.6.1.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : European Research Council
ID : 294340
Pays : International
Organisme : Medical Research Council
ID : MC_UP_1201/16
Pays : United Kingdom

Informations de copyright

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

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Auteurs

N B Martin-Cofreces (NB)

Immunology Service, Hospital Universitario de la Princesa, UAM, IIS-IP. Madrid, 28006 Spain. fsmadrid@salud.madrid.org jmv@cnb.csic.es noa.martin@salud.madrid.org.
Area of Vascular Pathophysiology, Laboratory of Intercellular Communication, Fundación Centro Nacional de Investigaciones Cardiovasculares-Carlos III, Madrid, 28029 Spain.
Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), 28029 Spain.

F J Chichon (FJ)

Department of Macromolecular Structure, Computational Systems Biology Group, Centro Nacional de Biotecnología (CNB-CSIC), Madrid, 28049, Spain.

E Calvo (E)

Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), 28029 Spain.
Laboratory of Cardiovascular Proteomics. Fundación Centro Nacional de Investigaciones Cardiovasculares-Carlos III, Madrid, 28029 Spain.

D Torralba (D)

Immunology Service, Hospital Universitario de la Princesa, UAM, IIS-IP. Madrid, 28006 Spain.
Area of Vascular Pathophysiology, Laboratory of Intercellular Communication, Fundación Centro Nacional de Investigaciones Cardiovasculares-Carlos III, Madrid, 28029 Spain.

E Bustos-Moran (E)

Immunology Service, Hospital Universitario de la Princesa, UAM, IIS-IP. Madrid, 28006 Spain.
Area of Vascular Pathophysiology, Laboratory of Intercellular Communication, Fundación Centro Nacional de Investigaciones Cardiovasculares-Carlos III, Madrid, 28029 Spain.

S G Dosil (SG)

Immunology Service, Hospital Universitario de la Princesa, UAM, IIS-IP. Madrid, 28006 Spain.
Area of Vascular Pathophysiology, Laboratory of Intercellular Communication, Fundación Centro Nacional de Investigaciones Cardiovasculares-Carlos III, Madrid, 28029 Spain.

A Rojas-Gomez (A)

Immunology Service, Hospital Universitario de la Princesa, UAM, IIS-IP. Madrid, 28006 Spain.
Area of Vascular Pathophysiology, Laboratory of Intercellular Communication, Fundación Centro Nacional de Investigaciones Cardiovasculares-Carlos III, Madrid, 28029 Spain.

E Bonzon-Kulichenko (E)

Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), 28029 Spain.
Laboratory of Cardiovascular Proteomics. Fundación Centro Nacional de Investigaciones Cardiovasculares-Carlos III, Madrid, 28029 Spain.

J A Lopez (JA)

Laboratory of Cardiovascular Proteomics. Fundación Centro Nacional de Investigaciones Cardiovasculares-Carlos III, Madrid, 28029 Spain.

J Otón (J)

Structural Studies Division, MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.

A Sorrentino (A)

ALBA Synchrotron Light Source, Cerdanyola del Vallès, Barcelona 08290, Spain.

J C Zabala (JC)

Departament of Molecular Biology, Facultad de Medicina, Universidad de Cantabria, Santander, 39005 Spain.

I Vernos (I)

Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr Aiguader 88, Barcelona, 08003, Spain.
Universitat Pompeu Fabra (UPF), Dr Aiguader 88, Barcelona 08003, Spain.
ICREA, Pg. Lluis Companys 23, Barcelona 08010, Spain.

J Vazquez (J)

Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), 28029 Spain.
Laboratory of Cardiovascular Proteomics. Fundación Centro Nacional de Investigaciones Cardiovasculares-Carlos III, Madrid, 28029 Spain.

J M Valpuesta (JM)

Department of Macromolecular Structure, Computational Systems Biology Group, Centro Nacional de Biotecnología (CNB-CSIC), Madrid, 28049, Spain. fsmadrid@salud.madrid.org jmv@cnb.csic.es noa.martin@salud.madrid.org.

F Sanchez-Madrid (F)

Immunology Service, Hospital Universitario de la Princesa, UAM, IIS-IP. Madrid, 28006 Spain. fsmadrid@salud.madrid.org jmv@cnb.csic.es noa.martin@salud.madrid.org.
Area of Vascular Pathophysiology, Laboratory of Intercellular Communication, Fundación Centro Nacional de Investigaciones Cardiovasculares-Carlos III, Madrid, 28029 Spain.
Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), 28029 Spain.

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Classifications MeSH