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

The chaperonin CCT controls T cell receptor-driven 3D configuration of centrioles.
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DOI:
10.1126/sciadv.abb7242
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发表时间:
2020-12
期刊:
影响因子:
13.6
通讯作者:
Sanchez-Madrid F
Sanchez-Madrid F
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Martin-Cofreces NB;Chichon FJ;Calvo E;Torralba D;Bustos-Moran E;Dosil SG;Rojas-Gomez A;Bonzon-Kulichenko E;Lopez JA;Otón J;Sorrentino A;Zabala JC;Vernos I;Vazquez J;Valpuesta JM;Sanchez-Madrid F

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真核分子伴侣蛋白TCP 1在免疫突触接触中驱动微管蛋白动力学和中心体结构T淋巴细胞活化需要与抗原呈递细胞形成免疫突触(IS)。IS处的膜受体、信号支架、微丝和微管的动力学决定T细胞活化和随后的免疫应答的效力。在这里,我们表明,胞质伴侣蛋白CCT(伴侣蛋白含TCP 1)控制的相互方向的中心粒和T细胞受体诱导的T淋巴细胞形成的IS微管蛋白动力学的极化的变化。CCT还控制T细胞的线粒体超微结构和代谢状态,调节微管蛋白的从头合成以及αβ-微管蛋白异源二聚体的翻译后修饰(聚谷氨酰化、乙酰化、Δ1和Δ2),微调微管蛋白动力学。这些变化最终决定了中心粒的功能和组织,如使用冷冻软X射线断层扫描对静息和刺激的原代T细胞进行三维重建所示。通过这种机制,CCT控制T细胞活化和极性。
Eukaryotic chaperonin-containing TCP1 drives tubulin dynamics and centrosome structure at immune synaptic contacts. 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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