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

Martin-Cofreces, Noa; Chichon, Francisco Javier; Calvo, Enrique; Torralba, Daniel; Bustos Moran, Eugenio; Dosil, Sara G.; Rojas-Gomez, Amelia; Bonzón-Kulichenko, Elena; Lopez, J. A.; Oton, Joaquin; Sorrentino, Andrea; Zabala, Juan C.; Vernos, Isabelle, 1959-; Vazquez, J.; Valpuesta, José M.; Sanchez-Madrid, Francisco

doi:http://dx.doi.org/10.1126/sciadv.abb7242

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

Citation

Martin-Cofreces NB, Chichon FJ, Calvo E, Torralba D, Bustos-Moran E, Dosil SG et al. The chaperonin CCT controls T cell receptor-driven 3D configuration of centrioles. Sci Adv. 2020 Dec 2;6(49):eabb7242. DOI:10.1126/sciadv.abb7242

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.