Sci Adv. 2020 Dec 2;6(49):eabb7242. Print 2020 Dec.
NB Martin-Cofreces , FJ Chichon, E Calvo, D Torralba, E Bustos-Moran, SG Dosil , A Rojas-Gomez , E Bonzon-Kulichenko, JA Lopez, J Otón, A Sorrentino, JC Zabala, I Vernos, J Vazquez, JM Valpuesta, F Sanchez-Madrid
Abstract
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.