Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/13242
The chaperonin CCT controls T cell receptor-driven 3D configuration of centrioles.
Martin-Cofreces, Noa B. CNIC | Chichon, F J | Calvo, Enrique CNIC | Torralba, Daniel CNIC | Bustos-Moran, Eugenio CNIC | Dosil, Sara G | Rojas-Gomez, A | Bonzon-Kulichenko, Elena CNIC | Lopez, Juan Antonio CNIC | Oton, J | Sorrentino, A | Zabala, J C | Vernos, Isabelle | Vazquez, Jesus CNIC | Valpuesta, Jose | Sanchez-Madrid, Francisco CNIC
Sci Adv. 2020; 6(49):eabb7242
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.