T cell activation requires mitochondrial translocation to the immunological synapse
- 4 September 2007
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 104 (36), 14418-14423
- https://doi.org/10.1073/pnas.0703126104
Abstract
T helper (Th) cell activation is required for the adaptive immune response. Formation of the immunological synapse (IS) between Th cells and antigen-presenting cells is essential for Th cell activation. IS formation induces the polarization and redistribution of many signaling molecules; however, very little is known about organelle redistribution during IS formation in Th cells. We show that formation of the IS induced cytoskeleton-dependent mitochondrial redistribution to the immediate vicinity of the IS. Using total internal reflection microscopy, we found that upon stimulation, the distance between the IS and mitochondria was decreased to values<200 nm. Consequently, mitochondria close to the IS took up more Ca2+ than the ones farther away from the IS. The redistribution of mitochondria to the IS was necessary to maintain Ca2+ influx across the plasma membrane and Ca2+-dependent Th cell activation. Our results suggest that mitochondria are part of the signaling complex at the IS and that their localization close to the IS is required for Th cell activation.Keywords
This publication has 42 references indexed in Scilit:
- Mitochondrial calcium signalling and cell death: Approaches for assessing the role of mitochondrial Ca2+ uptake in apoptosisCell Calcium, 2006
- The elementary unit of store-operated Ca2+ entry: local activation of CRAC channels by STIM1 at ER–plasma membrane junctionsThe Journal of cell biology, 2006
- Molecular identification of the CRAC channel by altered ion selectivity in a mutant of OraiNature, 2006
- CRACM1 Is a Plasma Membrane Protein Essential for Store-Operated Ca 2+ EntryScience, 2006
- A mutation in Orai1 causes immune deficiency by abrogating CRAC channel functionNature, 2006
- Newly generated T cell receptor microclusters initiate and sustain T cell activation by recruitment of Zap70 and SLP-76Nature Immunology, 2005
- Actin and agonist MHC–peptide complex–dependent T cell receptor microclusters as scaffolds for signalingThe Journal of Experimental Medicine, 2005
- STIM Is a Ca2+ Sensor Essential for Ca2+-Store-Depletion-Triggered Ca2+ InfluxCurrent Biology, 2005
- NFAT Signaling: Choreographing the Social Lives of CellsCell, 2002
- Synaptic pattern formation during cellular recognitionProceedings of the National Academy of Sciences of the United States of America, 2001