The mitochondrial fission factor dynamin-related protein 1 modulates T-cell receptor signalling at the immune synapse
The mitochondrial fission factor dynamin-related protein 1 modulates T-cell receptor signalling at the immune synapse
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DOI：
10.1038/emboj.2011.25
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发表时间：
2011-04-06
期刊：
影响因子：
11.4
通讯作者：
Sanchez-Madrid, Francisco
中科院分区：
文献类型：
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作者：
Baixauli, Francesc;Martin-Cofreces, Noa B.;Sanchez-Madrid, Francisco
在抗原特异性T细胞活化期间，线粒体向免疫突触附近移动。我们在这里表明，线粒体分裂因子动力蛋白相关蛋白1（Drp 1）停靠在线粒体，调节其定位和活动附近的周围超分子激活簇（pSMAC）的免疫突触的肌动蛋白丰富的环。响应于T细胞受体接合的线粒体再分配被Drp 1沉默、拟磷酸化突变体Drp 1 S637 D和Drp 1特异性抑制剂mdivi-1的表达所废除。此外，Drp 1敲低增强线粒体去极化和T细胞受体信号强度，但降低肌球蛋白磷酸化，ATP产生和T细胞受体组装在中央超分子活化簇（cSMAC）。我们的研究结果表明，Drp 1依赖的线粒体定位和活动控制T细胞活化的燃料中央超分子活化簇组装在免疫突触。The EMBO Journal（2011）30，1238-1250. doi：10.1038/daj.2011.25; 2011年2月15日在线发布
During antigen-specific T-cell activation, mitochondria mobilize towards the vicinity of the immune synapse. We show here that the mitochondrial fission factor dynamin-related protein 1 (Drp1) docks at mitochondria, regulating their positioning and activity near the actin-rich ring of the peripheral supramolecular activation cluster (pSMAC) of the immune synapse. Mitochondrial redistribution in response to T-cell receptor engagement was abolished by Drp1 silencing, expression of the phosphomimetic mutant Drp1S637D and the Drp1-specific inhibitor mdivi-1. Moreover, Drp1 knockdown enhanced mitochondrial depolarization and T-cell receptor signal strength, but decreased myosin phosphorylation, ATP production and T-cell receptor assembly at the central supramolecular activation cluster (cSMAC). Our results indicate that Drp1-dependent mitochondrial positioning and activity controls T-cell activation by fuelling central supramolecular activation cluster assembly at the immune synapse. The EMBO Journal (2011) 30, 1238-1250. doi: 10.1038/emboj.2011.25; Published online 15 February 2011