The mitochondrial fission factor dynamin-related protein 1 modulates T-cell receptor signalling at the immune synapse
Open Access
- 5 April 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 30 (7), 1238-1250
- https://doi.org/10.1038/emboj.2011.25
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. The EMBO Journal (2011) 30, 1238-1250. doi: 10.1038/emboj.2011.25; Published online 15 February 2011This publication has 48 references indexed in Scilit:
- Essential Role of Ubiquitin and TSG101 Protein in Formation and Function of the Central Supramolecular Activation ClusterImmunity, 2010
- T cell antigen receptor signaling and immunological synapse stability require myosin IIANature Immunology, 2009
- Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondriaProceedings of the National Academy of Sciences of the United States of America, 2008
- MTOC translocation modulates IS formation and controls sustained T cell signalingThe Journal of cell biology, 2008
- Chemical Inhibition of the Mitochondrial Division Dynamin Reveals Its Role in Bax/Bak-Dependent Mitochondrial Outer Membrane PermeabilizationDevelopmental Cell, 2008
- Fission and selective fusion govern mitochondrial segregation and elimination by autophagyThe EMBO Journal, 2008
- T cell activation requires mitochondrial translocation to the immunological synapseProceedings of the National Academy of Sciences of the United States of America, 2007
- Orchestration of lymphocyte chemotaxis by mitochondrial dynamicsThe Journal of Experimental Medicine, 2006
- T Cell Receptor-Proximal Signals Are Sustained in Peripheral Microclusters and Terminated in the Central Supramolecular Activation ClusterImmunity, 2006
- The Immunological Synapse: A Molecular Machine Controlling T Cell ActivationScience, 1999