Journal
SCIENCE ADVANCES
Volume 6, Issue 49, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abb7242
Keywords
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Categories
Funding
- ALBA [2015021148, 2016021638]
- Spanish Ministry of Economy and Competitiveness (MINECO) [SAF2017-82886-R, PID2019-105872GB-I00/AEI/10.13039/501100011033, BFU2016-75984, BIO2015-67580-P, PGC2018-097019-B-I00]
- Comunidad de Madrid [INFLAMUNE-S2017/BMD-23671, P2018/NMT-4389]
- Ramon Areces Foundation Ciencias de la Vida y la Salud
- Ayudas Fundacion BBVA a Equipos de Investigacion Cientifica
- PRB3 [IPT17/0019-ISCIII-SGEFI/ERDF]
- Fundacio Marato TV3 [122/C/2015]
- La Caixa Banking Foundation [HR17-00016, HR17-00247]
- Caixa Foundation
- Spanish Ministry of Science and Innovation [CSD2006-00023]
- Spanish Ministry of Economy and Competitiveness [BFU2012-37163, BFU2015-68726-P]
- Spanish Ministry of Science and Innovation
- Centro de Excelencia Severo Ochoa
- CERCA Programme/Generalitat de Catalunya
- CIBER Cardiovascular (Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III)
- CIBER Cardiovascular (Fondo Europeo de Desarrollo Regional FEDER)
- Spanish Ministry of Economy and Competitiveness (MINECO)
- Pro-CNIC Foundation
- Severo Ochoa Center of Excellence (MINECO) [SEV-20150505, SEV 2017-0712]
- [ERC-2011-AdG 294340-GENTRIS]
- MRC [MC_UP_1201/16] Funding Source: UKRI
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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 ultra-structure and the metabolic status of T cells, regulating the de novo synthesis of tubulin as well as posttranslational modifications (poly-glutamylation, acetylation, Delta 1 and Delta 2) of alpha beta-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.
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