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The mitochondrial fission factor dynamin‐related protein 1 modulates T‐cell receptor signalling at the immune synapse
Author(s) -
Baixauli Francesc,
MartínCófreces Noa B,
Morlino Giulia,
Carrasco Yolanda R,
CalabiaLinares Carmen,
Veiga Esteban,
Serrador Juan M,
SánchezMadrid Francisco
Publication year - 2011
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.25
Subject(s) - biology , dynamin , mitochondrial fission , immunological synapse , microbiology and biotechnology , dnm1l , synapse , receptor , immune system , immune receptor , mitochondrion , t cell , t cell receptor , neuroscience , immunology , endocytosis , genetics
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.