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

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...

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Detalles Bibliográficos
Autores: Martin-Cofreces, N. B., Chichon, F. J., Calvo, E., Torralba, D., Bustos-Moran, E., Dosil, S. G., Rojas-Gomez, A., Bonzon-Kulichenko, E., Lopez, J. A., Otón, J., Sorrentino, A., Zabala, J. C., Vernos, I., Vazquez, J., Valpuesta, J. M., Sánchez Madrid, Francisco
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/695519
Acceso en línea:http://hdl.handle.net/10486/695519
https://dx.doi.org/10.1126/sciadv.abb7242
Access Level:acceso abierto
Palabra clave:T lymphocyte
Antigen-presenting cells
Cytosolic chaperonin CCT
Mitochondrial ultrastructure
Polarity
Medicina
Descripción
Sumario: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.

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