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

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, ?1 and ?2) of ??-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.Cryo-SXT work was supported by ALBA Synchrotron standard proposals 2015021148 and 2016021638 to F.J.C., N.B.M.-C., and J.M.V. This study was supported by grants SAF2017-82886-R (to F.S.-M.), PID2019-105872GB-I00/AEI/10.13039/501100011033 (AEI/FEDER, UE), BFU2016-75984 (to J.M.V.), and BIO2015-67580-P and PGC2018-097019-B-I00 (to J.V.) from the Spanish Ministry of Economy and Competitiveness (MINECO), grants INFLAMUNE-S2017/BMD-23671 (to F.S.-M.) and P2018/NMT-4389 (to J.M.V.) from the Comunidad de Madrid, ERC-2011-AdG 294340-GENTRIS (to F.S.-M.), a 2019 grant from the Ramón Areces Foundation “Ciencias de la Vida y la Salud” and a 2018 grant from Ayudas Fundación BBVA a Equipos de Investigación Científica (to F.S.-M.), and grants PRB3 (IPT17/0019-ISCIII-SGEFI/ERDF), the Fundació Marató TV3 (grant 122/C/2015), and “La Caixa” Banking Foundation (HR17-00016 to FSM and HR17-00247 to J.V.). D.T. is supported by a PhD fellowship from La Caixa Foundation. Work in the Vernos lab was supported by the grant CSD2006-00023 from the Spanish Ministry of Science and Innovation and grants BFU2012-37163 and BFU2015-68726-P from the Spanish Ministry of Economy and Competitiveness. The CRG acknowledges support of the Spanish Ministry of Science and Innovation to the EMBL partnership, the Centro de Excelencia Severo Ochoa, and the CERCA Programme/Generalitat de Catalunya. CIBER Cardiovascular (Fondo de Investigación Sanitaria del Instituto de Salud Carlos III and co-funding by Fondo Europeo de Desarrollo Regional FEDER). The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Spanish Ministry of Economy and Competitiveness (MINECO) and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015- 0505). The Centro Nacional de Biotecnología (CNB) is a Severo Ochoa Center of Excellence (MINECO award SEV 2017-0712). Funding agencies have not intervened in the design of the studies, with no copyright over the stud

Transcellular communication at the immunological synapse: A vesicular traffic-mediated mutual exchange

The cell's ability to communicate with the extracellular environment, with other cells, and with itself is a crucial feature of eukaryotic organisms. In the immune system, T lymphocytes assemble a specialized structure upon contact with antigen-presenting cells bearing a peptide-major histocompatibility complex ligand, known as the immunological synapse (IS). The IS has been extensively characterized as a signaling platform essential for T-cell activation. Moreover, emerging evidence identifies the IS as a device for vesicular traffic-mediated cell-to-cell communication as well as an active release site of soluble molecules. Here, we will review recent advances in the role of vesicular trafficking in IS assembly and focused secretion of microvesicles at the synaptic area in naïve T cells and discuss the role of the IS in transcellular communication