The mitochondrial fission factor dynamin-related protein 1 modulates T-cell receptor signalling at the immune synapse.
EMBO J
; 30(7): 1238-50, 2011 Apr 06.
Article
em En
| MEDLINE
| ID: mdl-21326213
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos
/
Proteínas Mitocondriais
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Sinapses Imunológicas
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GTP Fosfo-Hidrolases
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Proteínas Associadas aos Microtúbulos
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Mitocôndrias
Limite:
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article