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Sci Adv ; 6(49)2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33268369

RESUMO

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 αß-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.


Assuntos
Chaperonina com TCP-1 , Tubulina (Proteína) , Centríolos/metabolismo , Chaperonina com TCP-1/metabolismo , Microtúbulos/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Tubulina (Proteína)/química
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