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PMID: 17726106 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

T cell activation requires mitochondrial translocation to the immunological synapse.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 104 ·No. 36 ·2007-09-04 ·Pages 14418-23

Quintana A, Schwindling C, Wenning AS, Becherer U, Rettig J, Schwarz EC, Hoth M

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.

MeSH Terms
Calcium/metabolism Cell Line Cell Proliferation Humans Lymphocyte Activation/immunology Microscopy, Electron Mitochondria/metabolism Receptors, Antigen, T-Cell/metabolism Signal Transduction Synapses/immunology T-Lymphocytes/cytology,immunology,metabolism
Chemicals
Receptors, Antigen, T-Cell Calcium
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Quintana Ariel
Department of Physiology, Saarland University, Gebäude 58/59, D-66421 Homburg, Germany. ptaqgo@uks.eu
Schwindling Christian
Wenning Anna S
Becherer Ute
Rettig Jens
Schwarz Eva C
Hoth Markus
References (42)
42 references, click to expand
  1. Synaptic pattern formation during cellular recognition.
    Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6548-53 PMID: 11371622
  2. Antigen decoding by T lymphocytes: from synapses to fate determination.
    Nat Immunol. 2001 Jun;2(6):487-92 PMID: 11376334
  3. Enhancement of calcium signalling dynamics and stability by delayed modulation of the plasma-membrane calcium-ATPase in human T cells.
    J Physiol. 2002 Jun 15;541(Pt 3):877-94 PMID: 12068047
  4. Store-operated Ca2+ entry depends on mitochondrial Ca2+ uptake.
    EMBO J. 2002 Dec 16;21(24):6744-54 PMID: 12485995
  5. Stable interactions between mitochondria and endoplasmic reticulum allow rapid accumulation of calcium in a subpopulation of mitochondria.
    J Biol Chem. 2003 Oct 3;278(40):39224-34 PMID: 12874292
  6. The immunological synapse balances T cell receptor signaling and degradation.
    Science. 2003 Nov 14;302(5648):1218-22 PMID: 14512504
  7. Ca2+ signaling in identified T-lymphocytes from human intestinal mucosa. Relation to hyporeactivity, proliferation, and inflammatory bowel disease.
    J Biol Chem. 2004 Feb 13;279(7):5641-7 PMID: 14585840
  8. Jurkat T cells and development of the T-cell receptor signalling paradigm.
    Nat Rev Immunol. 2004 Apr;4(4):301-8 PMID: 15057788
  9. New views of the immunological synapse: variations in assembly and function.
    Curr Opin Immunol. 2004 Jun;16(3):345-52 PMID: 15134784
  10. Apparent cytosolic calcium gradients in T-lymphocytes due to fura-2 accumulation in mitochondria.
    Cell Calcium. 2004 Aug;36(2):99-109 PMID: 15193858
  11. Mitochondrial localization as a determinant of capacitative Ca2+ entry in HeLa cells.
    Cell Calcium. 2004 Dec;36(6):499-508 PMID: 15488599
  12. Characterization of a monoclonal antibody which detects all murine alpha beta T cell receptors.
    J Immunol. 1989 Apr 15;142(8):2736-42 PMID: 2467936
  13. Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2(+)-ATPase.
    Proc Natl Acad Sci U S A. 1990 Apr;87(7):2466-70 PMID: 2138778
  14. Mitogen-regulated Ca2+ current of T lymphocytes is activated by depletion of intracellular Ca2+ stores.
    Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6295-9 PMID: 8392195
  15. Slow calcium-dependent inactivation of depletion-activated calcium current. Store-dependent and -independent mechanisms.
    J Biol Chem. 1995 Jun 16;270(24):14445-51 PMID: 7540169
  16. Characterization of T cell mutants with defects in capacitative calcium entry: genetic evidence for the physiological roles of CRAC channels.
    J Cell Biol. 1995 Nov;131(3):655-67 PMID: 7593187
  17. Axonal transport of mitochondria along microtubules and F-actin in living vertebrate neurons.
    J Cell Biol. 1995 Dec;131(5):1315-26 PMID: 8522592
  18. Making the T cell receptor go the distance: a topological view of T cell activation.
    Immunity. 1997 Apr;6(4):361-9 PMID: 9133415
  19. Mitochondrial regulation of store-operated calcium signaling in T lymphocytes.
    J Cell Biol. 1997 May 5;137(3):633-48 PMID: 9151670
  20. The immunological synapse: a molecular machine controlling T cell activation.
    Science. 1999 Jul 9;285(5425):221-7 PMID: 10398592
  21. Control of mitochondrial motility and distribution by the calcium signal: a homeostatic circuit.
    J Cell Biol. 2004 Nov 22;167(4):661-72 PMID: 15545319
  22. Store-operated calcium channels.
    Physiol Rev. 2005 Apr;85(2):757-810 PMID: 15788710
  23. Calcium-dependent activation of T-lymphocytes.
    Pflugers Arch. 2005 Apr;450(1):1-12 PMID: 15806400
  24. Tuning immune responses: diversity and adaptation of the immunological synapse.
    Nat Rev Immunol. 2005 Jul;5(7):532-45 PMID: 15999094
  25. STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx.
    Curr Biol. 2005 Jul 12;15(13):1235-41 PMID: 16005298
  26. Actin and agonist MHC-peptide complex-dependent T cell receptor microclusters as scaffolds for signaling.
    J Exp Med. 2005 Oct 17;202(8):1031-6 PMID: 16216891
  27. A dynamic view of the immunological synapse.
    Semin Immunol. 2005 Dec;17(6):400-10 PMID: 16266811
  28. Lymphocyte calcium signaling from membrane to nucleus.
    Nat Immunol. 2006 Jan;7(1):25-32 PMID: 16357855
  29. Newly generated T cell receptor microclusters initiate and sustain T cell activation by recruitment of Zap70 and SLP-76.
    Nat Immunol. 2005 Dec;6(12):1253-62 PMID: 16273097
  30. Subplasmalemmal mitochondria modulate the activity of plasma membrane Ca2+-ATPases.
    J Biol Chem. 2005 Dec 30;280(52):43198-208 PMID: 16216868
  31. A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function.
    Nature. 2006 May 11;441(7090):179-85 PMID: 16582901
  32. CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry.
    Science. 2006 May 26;312(5777):1220-3 PMID: 16645049
  33. The elementary unit of store-operated Ca2+ entry: local activation of CRAC channels by STIM1 at ER-plasma membrane junctions.
    J Cell Biol. 2006 Sep 11;174(6):815-25 PMID: 16966423
  34. Molecular identification of the CRAC channel by altered ion selectivity in a mutant of Orai.
    Nature. 2006 Sep 14;443(7108):226-9 PMID: 16921385
  35. Mitochondrial calcium signalling and cell death: approaches for assessing the role of mitochondrial Ca2+ uptake in apoptosis.
    Cell Calcium. 2006 Nov-Dec;40(5-6):553-60 PMID: 17074387
  36. Sustained activity of calcium release-activated calcium channels requires translocation of mitochondria to the plasma membrane.
    J Biol Chem. 2006 Dec 29;281(52):40302-9 PMID: 17056596
  37. Regulation of T-cell activation by the cytoskeleton.
    Nat Rev Immunol. 2007 Feb;7(2):131-43 PMID: 17259969
  38. NFAT signaling: choreographing the social lives of cells.
    Cell. 2002 Apr;109 Suppl:S67-79 PMID: 11983154
  39. Mitochondrial control of calcium-channel gating: a mechanism for sustained signaling and transcriptional activation in T lymphocytes.
    Proc Natl Acad Sci U S A. 2000 Sep 12;97(19):10607-12 PMID: 10973476
  40. On the dynamics of TCR:CD3 complex cell surface expression and downmodulation.
    Immunity. 2000 Nov;13(5):665-75 PMID: 11114379
  41. Calcium signaling mechanisms in T lymphocytes.
    Annu Rev Immunol. 2001;19:497-521 PMID: 11244045
  42. The immunological synapse and the actin cytoskeleton: molecular hardware for T cell signaling.
    Nat Immunol. 2000 Jul;1(1):23-9 PMID: 10881170
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0703126104
Email
ptaqgo@uks.eu
Published
2007-09-04
Epub
2007-00-28
Pages
14418-23
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1964825
Subset
IM
Corrections
CommentIn
PMID: 17881558
External Links
PubMed source DOI: 10.1073/pnas.0703126104 PMC Full Text View journal details
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