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The MTOC/Golgi Complex at the T-Cell Immunological Synapse

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The Golgi Apparatus and Centriole

Abstract

T cells effectively explore the tissue in search for antigens. When activated, they dedicate a big amount of energy and resources to arrange a complex structure called immunological synapse (IS), containing a particular distribution of molecules defined as supramolecular activation clusters (SMACs), and become polarized toward the target cell in a manner that channels the information specifically. This arrangement is symmetrical and requires the polarization of the MTOC and the Golgi to be operational, especially for the proper delivery of lytic granules and the recycling of molecules three dimensionally segregated at the clustered interface. Alternatively, after the productive encounter, T cells need to rearrange again to newly navigate through the tissue, changing back to a motile state called immunological kinapse (IK). In this IK state, the MTOC and the Golgi apparatus are repositioned and recruited at the back of the T cell to facilitate motility, while the established symmetry of the elements of the SMACs is broken and distributed in a different pattern. Both states, IS and IK, are interchangeable and are mainly orchestrated by the MTOC/Golgi complex, being critical for an effective immune response.

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References

  • Ariotti S, Beltman JB, Chodaczek G, Hoekstra ME, Van Beek AE, Gomez-Eerland R, Ritsma L, Van Rheenen J, Maree AF, Zal T, De Boer RJ, Haanen JB, Schumacher TN (2012) Tissue-resident memory CD8+ T cells continuously patrol skin epithelia To quickly recognize local antigen. Proc Natl Acad Sci U S A 109:19739–19744

    Article  CAS  Google Scholar 

  • Barcia C, Thomas CE, Curtin JF, King GD, Wawrowsky K, Candolfi M, Xiong WD, Liu C, Kroeger K, Boyer O, Kupiec-Weglinski J, Klatzmann D, Castro MG, Lowenstein PR (2006) In vivo mature immunological synapses forming SMACs mediate clearance of virally infected astrocytes from the brain. J Exp Med 203:2095–2107

    Article  CAS  Google Scholar 

  • Billadeau DD, Nolz JC, Gomez TS (2007) Regulation of T-cell activation by the cytoskeleton. Nat Rev Immunol 7:131–143

    Article  CAS  Google Scholar 

  • Blanchard N, Di Bartolo V, Hivroz C (2002) In the immune synapse, ZAP-70 controls T cell polarization and recruitment of signaling proteins but not formation of the synaptic pattern. Immunity 17:389–399

    Article  CAS  Google Scholar 

  • Cai E, Marchuk K, Beemiller P, Beppler C, Rubashkin MG, Weaver VM, Gerard A, Liu TL, Chen BC, Betzig E, Bartumeus F, Krummel MF (2017) Visualizing dynamic microvillar search and stabilization during ligand detection by T cells. Science 356:eaal3118

    Article  Google Scholar 

  • Cannon JL, Asperti-Boursin F, Letendre KA, Brown IK, Korzekwa KE, Blaine KM, Oruganti SR, Sperling AI, Moses ME (2013) PKCtheta regulates T cell motility via ezrin-radixin-moesin localization to the uropod. PLoS One 8:e78940

    Article  CAS  Google Scholar 

  • Carpier JM, Zucchetti AE, Bataille L, Dogniaux S, Shafaq-Zadah M, Bardin S, Lucchino M, Maurin M, Joannas LD, Magalhaes JG, Johannes L, Galli T, Goud B, Hivroz C (2018) Rab6-dependent retrograde traffic of LAT controls immune synapse formation and T cell activation. JExp Med 215:1245–1265

    Article  CAS  Google Scholar 

  • Chauveau A, Le Floc’h A, Bantilan NS, Koretzky GA, Huse M (2014) Diacylglycerol kinase alpha establishes T cell polarity by shaping diacylglycerol accumulation at the immunological synapse. Sci Signal 7:ra82

    Article  Google Scholar 

  • Crespo CL, Vernieri C, Keller PJ, Garre M, Bender JR, Wittbrodt J, Pardi R (2014) The PAR complex controls the spatiotemporal dynamics of F-actin and the MTOC in directionally migrating leukocytes. J Cell Sci 127:4381–4395

    Article  CAS  Google Scholar 

  • Diaz LR, Saavedra-Lopez E, Romarate L, Mitxitorena I, Casanova PV, Cribaro GP, Gallego JM, Perez-Valles A, Forteza-Vila J, Alfaro-Cervello C, Garcia-Verdugo JM, Barcia C Sr, Barcia C Jr (2018) Imbalance of immunological synapse-kinapse states reflects tumor escape to immunity in glioblastoma. JCI Insight 3:120757

    Article  Google Scholar 

  • Dustin ML (2005) A dynamic view of the immunological synapse. Semin Immunol 17:400–410

    Article  CAS  Google Scholar 

  • Dustin ML (2007) Cell adhesion molecules and actin cytoskeleton at immune synapses and kinapses. Curr Opin Cell Biol 19:529–533

    Article  CAS  Google Scholar 

  • Dustin ML (2008) T-cell activation through immunological synapses and kinapses. Immunol Rev 221:77–89

    Article  CAS  Google Scholar 

  • Dustin ML (2010) The immunological synapse. In: Bradshaw RA, Dennis EA (eds) Handbook of cell signaling. Academic, London

    Google Scholar 

  • Dustin ML, Chakraborty AK, Shaw AS (2010) Understanding the structure and function of the immunological synapse. Cold Spring Harb Perspect Biol 2:a002311

    Article  CAS  Google Scholar 

  • Etienne-Manneville S (2004) Cdc42–the centre of polarity. J Cell Sci 117:1291–1300

    Article  CAS  Google Scholar 

  • Evans R, Patzak I, Svensson L, De Filippo K, Jones K, Mcdowall A, Hogg N (2009) Integrins in immunity. J Cell Sci 122:215–225

    Article  CAS  Google Scholar 

  • Franciszkiewicz K, Le Floc’h A, Boutet M, Vergnon I, Schmitt A, Mami-Chouaib F (2013) CD103 or LFA-1 engagement at the immune synapse between cytotoxic T cells and tumor cells promotes maturation and regulates T-cell effector functions. Cancer Res 73:617–628

    Article  CAS  Google Scholar 

  • Fritzsche M, Dustin ML (2018) Organization of immunological synapses and kinapses. In: Putterman C, Cowburn D, Almo S (eds) Structural biology in immunology. Academic, London

    Google Scholar 

  • Grakoui A, Bromley SK, Sumen C, Davis MM, Shaw AS, Allen PM, Dustin ML (1999) The immunological synapse: a molecular machine controlling T cell activation. Science 285:221–227

    Article  CAS  Google Scholar 

  • Holdorf AD, Lee KH, Burack WR, Allen PM, Shaw AS (2002) Regulation of Lck activity by CD4 and CD28 in the immunological synapse. Nat Immunol 3:259–264

    Article  CAS  Google Scholar 

  • Huppa JB, Davis MM (2003) T-cell-antigen recognition and the immunological synapse. Nat Rev Immunol 3:973–983

    Article  CAS  Google Scholar 

  • Huse M, Lillemeier BF, Kuhns MS, Chen DS, Davis MM (2006) T cells use two directionally distinct pathways for cytokine secretion. Nat Immunol 7:247–255

    Article  CAS  Google Scholar 

  • Huse M, Le Floc’h A, Liu X (2013) From lipid second messengers to molecular motors: microtubule-organizing center reorientation in T cells. Immunol Rev 256:95–106

    Article  CAS  Google Scholar 

  • Johnson KG, Bromley SK, Dustin ML, Thomas ML (2000) A supramolecular basis for CD45 tyrosine phosphatase regulation in sustained T cell activation. Proc Natl Acad Sci U S A 97:10138–10143

    Article  CAS  Google Scholar 

  • Kaizuka Y, Douglass AD, Varma R, Dustin ML, Vale RD (2007) Mechanisms for segregating T cell receptor and adhesion molecules during immunological synapse formation in Jurkat T cells. Proc Natl Acad Sci U S A 104:20296–20301

    Article  CAS  Google Scholar 

  • Kloc M, Kubiak JZ, Li XC, Ghobrial RM (2014) The newly found functions of MTOC in immunological response. J Leukoc Biol 95:417–430

    Article  Google Scholar 

  • Kuhn JR, Poenie M (2002) Dynamic polarization of the microtubule cytoskeleton during CTL-mediated killing. Immunity 16:111–121

    Article  CAS  Google Scholar 

  • Lee KH, Holdorf AD, Dustin ML, Chan AC, Allen PM, Shaw AS (2002) T cell receptor signaling precedes immunological synapse formation. Science 295:1539–1542

    Article  CAS  Google Scholar 

  • Lively S, Schlichter LC (2013) The microglial activation state regulates migration and roles of matrix-dissolving enzymes for invasion. J Neuroinflammation 10:75

    Article  CAS  Google Scholar 

  • Lu YC, Robbins PF (2016) Cancer immunotherapy targeting neoantigens. Semin Immunol 28:22–27

    Article  CAS  Google Scholar 

  • Maccari I, Zhao R, Peglow M, Schwarz K, Hornak I, Pasche M, Quintana A, Hoth M, Qu B, Rieger H (2016) Cytoskeleton rotation relocates mitochondria to the immunological synapse and increases calcium signals. Cell Calcium 60:309–321

    Article  CAS  Google Scholar 

  • Mitxitorena I, Saavedra E, Barcia C (2015) Kupfer-type immunological synapses in vivo: raison D’etre of SMAC. Immunol Cell Biol 93:51–56

    Article  CAS  Google Scholar 

  • Monks CR, Freiberg BA, Kupfer H, Sciaky N, Kupfer A (1998) Three-dimensional segregation of supramolecular activation clusters in T cells. Nature 395:82–86

    Article  CAS  Google Scholar 

  • Moreau HD, Lemaitre F, Terriac E, Azar G, Piel M, Lennon-Dumenil AM, Bousso P (2012) Dynamic in situ cytometry uncovers T cell receptor signaling during immunological synapses and kinapses in vivo. Immunity 37:351–363

    Article  CAS  Google Scholar 

  • Moreau HD, Lemaitre F, Garrod KR, Garcia Z, Lennon-Dumenil AM, Bousso P (2015) Signal strength regulates antigen-mediated T-cell deceleration by distinct mechanisms to promote local exploration or arrest. Proc Natl Acad Sci U S A 112:12151–12156

    Article  CAS  Google Scholar 

  • Nath S, Christian L, Tan SY, Ki S, Ehrlich LI, Poenie M (2016) Dynein separately partners with NDE1 and dynactin To orchestrate T cell focused secretion. J Immunol 197:2090–2101

    Article  CAS  Google Scholar 

  • Negulescu PA, Krasieva TB, Khan A, Kerschbaum HH, Cahalan MD (1996) Polarity of T cell shape, motility, and sensitivity to antigen. Immunity 4:421–430

    Article  CAS  Google Scholar 

  • Quintana A, Pasche M, Junker C, Al-Ansary D, Rieger H, Kummerow C, Nunez L, Villalobos C, Meraner P, Becherer U, Rettig J, Niemeyer BA, Hoth M (2011) Calcium microdomains at the immunological synapse: how ORAI channels, mitochondria and calcium pumps generate local calcium signals for efficient T-cell activation. EMBO J 30:3895–3912

    Article  CAS  Google Scholar 

  • Ratner S, Sherrod WS, Lichlyter D (1997) Microtubule retraction into the uropod and its role in T cell polarization and motility. J Immunol 159:1063–1067

    CAS  PubMed  Google Scholar 

  • Stinchcombe JC, Bossi G, Booth S, Griffiths GM (2001) The immunological synapse of CTL contains a secretory domain and membrane bridges. Immunity 15:751–761

    Article  CAS  Google Scholar 

  • Stinchcombe JC, Majorovits E, Bossi G, Fuller S, Griffiths GM (2006) Centrosome polarization delivers secretory granules to the immunological synapse. Nature 443:462–465

    Article  CAS  Google Scholar 

  • Tsun A, Qureshi I, Stinchcombe JC, Jenkins MR, De La Roche M, Kleczkowska J, Zamoyska R, Griffiths GM (2011) Centrosome docking at the immunological synapse is controlled by Lck signaling. J Cell Biol 192:663–674

    Article  CAS  Google Scholar 

  • Vicente-Manzanares M, Sanchez-Madrid F (2004) Role of the cytoskeleton during leukocyte responses. Nat Rev Immunol 4:110–122

    Article  CAS  Google Scholar 

  • Vicente-Manzanares M, Ma X, Adelstein RS, Horwitz AR (2009) Non-muscle myosin II takes centre stage in cell adhesion and migration. Nat Rev Mol Cell Biol 10:778–790

    Article  CAS  Google Scholar 

  • Weninger W, Biro M, Jain R (2014) Leukocyte migration in the interstitial space of non-lymphoid organs. Nat Rev Immunol 14:232–246

    Article  CAS  Google Scholar 

  • Yarchoan M, Johnson BA 3rd, Lutz ER, Laheru DA, Jaffee EM (2017) Targeting neoantigens to augment antitumour immunity. Nat Rev Cancer 17:209–222

    Article  CAS  Google Scholar 

  • Yu Y, Smoligovets AA, Groves JT (2013) Modulation of T cell signaling by the actin cytoskeleton. J Cell Sci 126:1049–1058

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the Spanish Ministry of Economy and Competitiveness, and the European Regional Development Fund (Fondo Europeo de Desarrollo Regional, FEDER) (Reference Grants: RYC-2010-06729, SAF2013-45178-P, and SAF2015-64123-P), Generalitat de Catalunya (Reference Grant: 2014 SGR-984) and by the Asociación Española Contra el Cancer (AECC).

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Correspondence to Carlos Barcia .

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Roig-Martinez, M., Saavedra-Lopez, E., Casanova, P.V., Cribaro, G.P., Barcia, C. (2019). The MTOC/Golgi Complex at the T-Cell Immunological Synapse. In: Kloc, M. (eds) The Golgi Apparatus and Centriole. Results and Problems in Cell Differentiation, vol 67. Springer, Cham. https://doi.org/10.1007/978-3-030-23173-6_9

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