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

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, ?1 and ?2) of ??-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.

SUBMITTER: Martin-Cofreces NB

PROVIDER: S-EPMC7821906 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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

Martin-Cofreces N B NB Chichon F J FJ Calvo E E Torralba D D Bustos-Moran E E Dosil S G SG Rojas-Gomez A A Bonzon-Kulichenko E E Lopez J A JA Otón J J Sorrentino A A Zabala J C JC Vernos I I Vazquez J J Valpuesta J M JM Sanchez-Madrid F F

Science advances 20201202 49

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 lymphocy ...[more]

PMID: 33268369

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Project description:Please provide an overall description of your study, think something similar in scope to the manuscript abstractCell proteostasiCell proteostasis includes gene transcription, protein translation, folding of de novo proteins, post-translational modification, secretion, degradation and recycling. By profiling the proteome of extracellular vesicles (EVs) from T cells, we have found the chaperonin complex CCT, involved in the correct folding of particular proteins. By limiting CCT cell-content by siRNA, cells undergo altered lipid composition and metabolic rewiring towards a lipid-dependent metabolism, with increased activity of peroxisomes and mitochondria. This is due to dysregulation of the dynamics of interorganellar contacts between lipid droplets, mitochondria, peroxisomes and the endolysosomal system. This process accelerates the biogenesis of multivesicular bodies leading to higher EV production through the dynamic regulation of microtubule-based kinesin motors. These findings connect proteostasis with lipid metabolism through an unexpected role of CCT.s includes gene transcription, protein translation, folding of de novo proteins, post-translational modification, secretion, degradation and recycling. By profiling the proteome of extracellular vesicles (EVs) from T cells, we have found the chaperonin complex CCT, involved in the correct folding of particular proteins. By limiting CCT cell-content by siRNA, cells undergo altered lipid composition and metabolic rewiring towards a lipid-dependent metabolism, with increased activity of peroxisomes and mitochondria. This is due to dysregulation of the dynamics of interorganellar contacts between lipid droplets, mitochondria, peroxisomes and the endolysosomal system. This process accelerates the biogenesis of multivesicular bodies leading to higher EV production through the dynamic regulation of microtubule-based kinesin motors. These findings connect proteostasis with lipid metabolism through an unexpected role of CCT.

Dataset Information

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

Publications

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

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