The chaperonin CCT controls T cell receptor–driven 3D configuration of centrioles
Noa B. Martín‐Cófreces, Francisco Javier Chichón, Enrique Calvo, Daniel Torralba, Eugenio Bustos‐Morán, Sara G. Dosil, Amelia Rojas‐Gómez, Elena Bonzón‐Kulichenko, Juan Antonio López, Joaquı́n Otón, Andrea Sorrentino, Juan Carlos Zabala, Isabelle Vernos, Jesús Vázquez, José Valpuesta, Francisco Sánchez‐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.