Sci. STKE, 11 September 2007
Immunology Mitochondria at the Immunological Synapse
Nancy R. Gough
Science's STKE, AAAS, Washington, DC 20005, USA
Quintana et al. noted that beads coated with antibodies to CD3, a constituent of the T cell receptor (TCR) complex, produced a larger and more sustained calcium signal in the Jurkat T cell line and primary human T cells than did the same antibodies in solution. This difference correlated with the antibody-coated beads ability to stimulate the formation of the immune synapse, a macromolecular structure that forms at the plasma membrane at the site of TCR activation and that is involved in T cell activation. Calcium influx across the plasma membrane in response to TCR activation involves the activation of calcium release-activated calcium (CRAC) channels, the Orai1 channels, in response to depletion of calcium from intracellular stores. Quintana et al. found that when mitochondrial calcium uptake was pharmacologically inhibited, calcium signaling was decreased in response to the antibody-coated beads. Indeed, TCR activation triggered the relocation of mitochondria to within 200 nm of the plasma membrane at the site of the immune synapse (based on total internal reflection microscopy), and these mitochondria that were close to the immune synapse exhibited enhanced calcium uptake compared with that of mitochondria distant from the immune synapse. The authors suggest that the relocation of the mitochondria to the immune synapse and their uptake of calcium prevent calcium-induced inactivation of the Orai1 channels, thereby allowing sustained calcium influx in response to stimuli that induce the formation of the immune synapse.
A. Quintana, C. Schwindling, A. S. Wenning, U. Becherer, J. Rettig, E. C. Schwarz, M. Hoth, T cell activation requires mitochondrial translocation to the immunological synapse. Proc. Natl. Acad. Sci. U.S.A. 104, 14418-14423 (2007). [Abstract] [Full Text]
Citation: N. R. Gough, Mitochondria at the Immunological Synapse. Sci. STKE 2007, tw329 (2007).
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