The mitochondrial fission factor dynamin-related protein 1 modulates T-cell receptor signalling at the immune synapse

被引：142

作者：

Baixauli, Francesc ^{[1
,2
]}

Martin-Cofreces, Noa B. ^{[1
,2
]}

Morlino, Giulia ^{[1
]}

Carrasco, Yolanda R. ^{[3
]}

Calabia-Linares, Carmen ^{[1
]}

Veiga, Esteban ^{[1
,4
]}

Serrador, Juan M. ^{[5
]}

Sanchez-Madrid, Francisco ^{[1
,2
]}

机构：

[1] Univ Autonoma Madrid, Serv Inmunol, Hosp Univ Princesa, Inst Invest Sanitaria Princesa IIS IP, Madrid, Spain

[2] Ctr Nacl Invest Cardiovasc, Dept Biol Vasc & Inflamac, Madrid, Spain

[3] CSIC, Dept Inmunol & Oncol, Ctr Nacl Biotecnol, Madrid, Spain

[4] CSIC, Dept Biol Mol & Celular, Ctr Nacl Biotecnol, Madrid, Spain

[5] UAM CSIC, Dept Biol Celular & Inmunol, Ctr Biol Mol Severo Ochoa, Madrid, Spain

来源：

EMBO JOURNAL | 2011年 / 30卷 / 07期

关键词：

cell signalling; fission factor; immune synapse; mitochondria; T-cell receptor; SUPRAMOLECULAR ACTIVATION CLUSTER; GTPASE EFFECTOR DOMAIN; IMMUNOLOGICAL SYNAPSE; CYTOPLASMIC DYNEIN; AXONAL-TRANSPORT; DRP1; FUSION; TRANSLOCATION; CYTOSKELETON; SEGREGATION;

D O I：

10.1038/emboj.2011.25

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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

引用

页码：1238 / 1250

页数：13

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