Orchestrating cytoskeleton and intracellular vesicle traffic to build functional immunological synapses

Immunological Reviews

Volumn 256, Issue 1, 2013, Pages 118-132

  Soares, Helena ^a,b   Lasserre, Rémi ^a,b   Alcover, Andrés ^a,b  

^a INSTITUT PASTEUR   (France)

^b CNRS   (France)

Author keywords

Actin; HIV; Immunological synapse; Microtubules; T cell antigen receptor; Vesicle traffic

Indexed keywords

ACTIN; EZRIN; FOCAL ADHESION KINASE; GUANINE NUCLEOTIDE EXCHANGE FACTOR; LYMPHOCYTE ANTIGEN RECEPTOR; MEMBRANE PHOSPHOLIPID; MEMBRANE PROTEIN; MOESIN; PHOSPHATIDYLINOSITOL 3 KINASE; RADIXIN; REGULATOR PROTEIN; T LYMPHOCYTE RECEPTOR;

ACTIN FILAMENT; ACTIN POLYMERIZATION; ANTIGEN RECOGNITION; ARTICLE; CELL FUNCTION; CELL MIGRATION; CYTOSKELETON; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; IMMUNOLOGICAL SYNAPSE; INTRACELLULAR SIGNALING; MICROTUBULE; MITOCHONDRION; POLARIZATION; PRIORITY JOURNAL; PROTEIN EXPRESSION; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION;

ACTIN; HIV; IMMUNOLOGICAL SYNAPSE; MICROTUBULES; T-CELL ANTIGEN RECEPTOR; VESICLE TRAFFIC;

ANIMALS; BIOLOGICAL TRANSPORT; CYTOSKELETON; HIV; HUMANS; IMMUNOLOGICAL SYNAPSES; RECEPTORS, ANTIGEN, T-CELL; SIGNAL TRANSDUCTION; T-LYMPHOCYTE SUBSETS; TRANSPORT VESICLES;

EID: 84885366836     PISSN: 01052896     EISSN: 1600065X     Source Type: Journal    
DOI: 10.1111/imr.12110     Document Type: Article

References (151)

1. Burkhardt JK, Carrizosa E, Shaffer MH. The actin cytoskeleton in T cell activation. Annu Rev Immunol 2008;26:233-259.
2. Lasserre R, Alcover A. Cytoskeletal cross-talk in the control of T cell antigen receptor signaling. FEBS Lett 2010;584:4845-4850.
3. Martin-Cofreces NB, Alarcon B, Sanchez-Madrid F. Tubulin and actin interplay at the T cell and antigen-presenting cell interface. Front Immunol 2011;2:24.
4. Gomez TS, Billadeau DD. T cell activation and the cytoskeleton: you can't have one without the other. Adv Immunol 2008;97:1-64.
5. Valitutti S, Dessing M, Aktories K, Gallati H, Lanzavecchia A. Sustained signaling leading to T cell activation results from prolonged T cell receptor occupancy. Role of T cell actin cytoskeleton. J Exp Med 1995;181:577-584.
6. Campi G, Varma R, Dustin ML. Actin and agonist MHC-peptide complex-dependent T cell receptor microclusters as scaffolds for signaling. J Exp Med 2005;202:1031-1036.
7. Geiger B, Rosen D, Berke G. Spatial relationships of microtubule-organizing centers and the contact area of cytotoxic T lymphocytes and target cells. J Cell Biol 1982;95:137-143.
8. Kupfer A, Dennert G. Reorientation of the microtubule organizing center and the Golgi apparatus in cloned cytotoxic lymphocytes triggered by binding to lysable target cells. J Immunol 1984;133:2762-2766.
9. Stinchcombe JC, Majorovits E, Bossi G, Fuller S, Griffiths GM. Centrosome polarization delivers secretory granules to the immunological synapse. Nature 2006;443:462-465.
10. Kuhn JR, Poenie M. Dynamic polarization of the microtubule cytoskeleton during CTL-mediated killing. Immunity 2002;16:111-121.
11. Lasserre R, et al. Ezrin tunes T-cell activation by controlling Dlg1 and microtubule positioning at the immunological synapse. EMBO J 2010;29:2301-2314.
12. Lowin-Kropf B, Shapiro VS, Weiss A. Cytoskeletal polarization of T cells is regulated by an immunoreceptor tyrosine-based activation motif-dependent mechanism. J Cell Biol 1998;140:861-871.
13. Martin-Cofreces NB, et al. Role of Fyn in the rearrangement of tubulin cytoskeleton induced through TCR. J Immunol 2006;176:4201-4207.
14. Tsun A, et al. Centrosome docking at the immunological synapse is controlled by Lck signaling. J Cell Biol 2011;192:663-674.
15. Blanchard N, Di Bartolo V, Hivroz C. In the immune synapse, ZAP-70 controls T cell polarization and recruitment of signaling proteins but not formation of the synaptic pattern. Immunity 2002;17:389-399.
16. Combs J, et al. Recruitment of dynein to the Jurkat immunological synapse. Proc Natl Acad Sci USA 2006;103:14883-14888.
17. Quann EJ, Liu X, Altan-Bonnet G, Huse M. A cascade of protein kinase C isozymes promotes cytoskeletal polarization in T cells. Nat Immunol 2011;12:647-654.
18. Stowers L, Yelon D, Berg LJ, Chant J. Regulation of the polarization of T cells toward antigen-presenting cells by Ras-related GTPase Cdc42. Proc Natl Acad Sci USA 1995;92:5027-5031.
19. Gomez TS, Kumar K, Medeiros RB, Shimizu Y, Leibson PJ, Billadeau DD. Formins regulate the actin-related protein 2/3 complex-independent polarization of the centrosome to the immunological synapse. Immunity 2007;26:177-190.
20. Chemin K, et al. Cytokine secretion by CD4+ T cells at the immunological synapse requires Cdc42-dependent local actin remodeling but not microtubule organizing center polarity. J Immunol 2012;189:2159-2168.
21. Etienne-Manneville S. Polarity proteins in migration and invasion. Oncogene 2008;27:6970-6980.
22. Andres-Delgado L, et al. INF2 promotes the formation of detyrosinated microtubules necessary for centrosome reorientation in T cells. J Cell Biol 2012;198:1025-1037.
23. Serrador JM, Cabrero JR, Sancho D, Mittelbrunn M, Urzainqui A, Sanchez-Madrid F. HDAC6 deacetylase activity links the tubulin cytoskeleton with immune synapse organization. Immunity 2004;20:417-428.
24. Martin-Cofreces NB, et al. MTOC translocation modulates IS formation and controls sustained T cell signaling. J Cell Biol 2008;182:951-962.
25. Quann EJ, Merino E, Furuta T, Huse M. Localized diacylglycerol drives the polarization of the microtubule-organizing center in T cells. Nat Immunol 2009;10:627-635.
26. Bunnell SC, Kapoor V, Trible RP, Zhang W, Samelson LE. Dynamic actin polymerization drives T cell receptor-induced spreading: a role for the signal adaptor LAT. Immunity 2001;14:315-329.
27. Das V, et al. Activation-induced polarized recycling targets T cell antigen receptors to the immunological synapse; involvement of SNARE complexes. Immunity 2004;20:577-588.
28. Hashimoto-Tane A, et al. Dynein-driven transport of T cell receptor microclusters regulates immune synapse formation and T cell activation. Immunity 2011;34:919-931.
29. Martin-Cofreces NB, et al. End-binding protein 1 controls signal propagation from the T cell receptor. EMBO J 2012;31:4140-4152.
30. Arpin M, Algrain M, Louvard D. Membrane-actin microfilament connections: an increasing diversity of players related to band 4.1. Curr Op Cell Biol 1994;6:136-141.
31. Bretscher A, Chambers D, Nguyen R, Reczek D. ERM-Merlin and EBP50 protein families in plasma membrane organization and function. Ann Rev Cell Dev Biol 2000;16:113-143.
32. Serrador JM, et al. CD43 interacts with moesin and ezrin and regulates its distribution to the uropods of T lymphocytes at the cell-cell contacts. Blood 1998;91:4632-4644.
33. Serrador JM, et al. Moesin interacts with the cytoplasmic region of intercellular adhesion molecule-3 and is redistributed to the uropod of T lymphocytes during cell polarization. J Cell Biol 1997;138:1409-1423.
34. Roumier A, et al. The membrane-microfilament linker ezrin is involved in the formation of the immunological synapse and in T cell activation. Immunity 2001;15:715-728.
35. Delon J, Kaibuchi K, Germain RN. Exclusion of CD43 from the immunological synapse is mediated by phosphorylation-regulated relocation of the cytoskeletal adaptor moesin. Immunity 2001;15:691-701.
36. Allenspach EJ, et al. ERM-dependent movement of CD43 defines a novel protein complex distal to the immunological synapse. Immunity 2001;15:739-750.
37. van der Merwe PA, Davis SJ, Shaw AS, Dustin ML. Cytoskeletal polarization and redistribution of cell-surface molecules during T cell antigen recognition. Semin Immunol 2000;12:5-21.
38. Savage ND, Kimzey SL, Bromley SK, Johnson KG, Dustin ML, Green JM. Polar redistribution of the sialoglycoprotein CD43: implications for T cell function. J Immunol 2002;168:3740-3746.
39. Tong J, et al. CD43 regulation of T cell activation is not through steric inhibition of T cell-APC interactions but through an intracellular mechanism. J Exp Med 2004;199:1277-1283.
40. Gautreau A, Louvard D, Arpin M. ERM proteins and NF2 tumor suppressor: the yin and yang of cortical actin organization and cell growth signaling. Curr Op Cell Biol 2002;14:104-109.
41. Belkina NV, Liu Y, Hao JJ, Karasuyama H, Shaw S. LOK is a major ERM kinase in resting lymphocytes and regulates cytoskeletal rearrangement through ERM phosphorylation. Proc Natl Acad Sci USA 2009;106:4707-4712.
42. Matsui T, et al. Rho-kinase phosphorylates COOH-terminal threonines of ezrin/radixin/moesin (ERM) proteins and regulates their head to tail association. J Cell Biol 1998;3:647-657.
43. Pietromonaco SF, Simons PC, Altman A, Elias L. Protein kinase C-θ phosphorylation of moesin in the actin-binding sequence. J Biol Chem 1998;273:7594-7603.
44. Faure S, et al. ERM proteins regulate cytoskeleton relaxation promoting T cell-APC conjugation. Nat Immunol 2004;5:272-279.
45. Brown MJ, et al. Chemokine stimulation of human peripheral blood T lymphocytes induces rapid dephosphorylation of ERM proteins, which facilitates loss of microvilli and polarization. Blood 2003;102:3890-3899.
46. Ilani T, Khanna C, Zhou M, Veenstra TD, Bretscher A. Immune synapse formation requires ZAP-70 recruitment by ezrin and CD43 removal by moesin. J Cell Biol 2007;179:733-746.
47. Treanor B, et al. The membrane skeleton controls diffusion dynamics and signaling through the B cell receptor. Immunity 2010;32:187-199.
48. Arpin M, Chirivino D, Naba A, Zwaenepoel I. Emerging role for ERM proteins in cell adhesion and migration. Cell Adh Migr 2011;5:199-206.
49. Fievet B, Louvard D, Arpin M. ERM proteins in epithelial cell organization and functions. Biochim Biophys Acta 2007;1773:653-660.
50. Charrin S, Alcover A. Role of ERM (ezrin-radixin-moesin) proteins in T lymphocyte polarization, Immune synapse Formation and in T cell receptor-mediated signaling. Front Biosc 2006;11:1987-1997.
51. Shaffer MH, et al. Ezrin and moesin function together to promote T cell activation. J Immunol 2009;182:1021-1032.
52. Grakoui A, et al. The immunological synapse: a molecular machine controlling T cell activation. Science 1999;285:221-227.
53. Bunnell SC, et al. T cell receptor ligation induces the formation of dynamically regulated signaling assemblies. J Cell Biol 2002;158:1263-1275.
54. Schnyder T, et al. B cell receptor-mediated antigen gathering requires ubiquitin ligase cbl and adaptors grb2 and dok-3 to recruit Dynein to the signaling microcluster. Immunity 2011;34:905-918.
55. Manneville JB, Jehanno M, Etienne-Manneville S. Dlg1 binds GKAP to control dynein association with microtubules, centrosome positioning, and cell polarity. J Cell Biol 2010;191:585-598.
56. Round JL, Humphries LA, Tomassian T, Mittelstadt P, Zhang M, Miceli MC. Scaffold protein Dlgh1 coordinates alternative p38 kinase activation, directing T cell receptor signals toward NFAT but not NF-kappaB transcription factors. Nat Immunol 2007;8:154-161.
57. Lue RA, Brandin E, Chan EP, Branton D. Two independent domains of hDlg are sufficient for subcellular targeting: the PDZ1-2 conformational unit and an alternatively spliced domain. J Cell Biol 1996;135:1125-1137.
58. Fukata M, et al. Rac1 and Cdc42 capture microtubules through IQGAP1 and CLIP-170. Cell 2002;109:873-885.
59. Gorman JA, et al. The cytoskeletal adaptor protein IQGAP1 regulates TCR-mediated signaling and filamentous actin dynamics. J Immunol 2012;188:6135-6144.
60. Das V, et al. Membrane-cytoskeleton interactions during the formation of the immunological synapse and subsequent T cell activation. Immunol Revs 2002;189:123-135.
61. Nal B, et al. Coronin-1 expression in T lymphocytes: insights into protein function during T cell development and activation. Int Immunol 2004;16:231-240.
62. Foger N, Rangell L, Danilenko DM, Chan AC. Requirement for coronin 1 in T lymphocyte trafficking and cellular homeostasis. Science 2006;313:839-842.
63. Haraldsson MK, et al. The lupus-related Lmb3 locus contains a disease-suppressing Coronin-1A gene mutation. Immunity 2008;28:40-51.
64. Mueller P, et al. Regulation of T cell survival through coronin-1-mediated generation of inositol-1, 4, 5-trisphosphate and calcium mobilization after T cell receptor triggering. Nat Immunol 2008;9:424-431.
65. Mugnier B, et al. Coronin-1A links cytoskeleton dynamics to TCR alpha beta-induced cell signaling. PLoS ONE 2008;3:e3467.
66. Soares H, et al. Regulated vesicle fusion generates signaling nanoterritiries that control T-cell activation at the immunological synapse. J Exp Med 2013; in press.
67. Favier B, Burroughs NJ, Wedderburn L, Valitutti S. TCR dynamics on the surface of living T cells. Int Immunol 2001;13:1525-1532.
68. Wülfing C, Davis MM. A receptor/cytoskeletal movement triggered by costimulation during T cell activation. Science 1998;282:2266-2269.
69. Douglass AD, Vale RD. Single-molecule microscopy reveals plasma membrane microdomains created by protein-protein networks that exclude or trap signaling molecules in T cells. Cell 2005;121:937-950.
70. Batista A, Millan J, Mittelbrunn M, Sanchez-Madrid F, Alonso MA. Recruitment of transferrin receptor to immunological synapse in response to TCR engagement. J Immunol 2004;172:6709-6714.
71. Alcover A, Alarcón B. Internalization and intracellular fate of TCR-CD3 complexes. Crit Rev Immunol 2000;20:325-346.
72. Sudhof TC, Rizo J. Synaptic vesicle exocytosis. Cold Spring Harb Perspect: Biol, 2011:3.
73. Kappes J, Alarcón B, Regueiro JR. T lymphocyte receptor deficiencies. Curr Op Immunol 1995;7:441-447.
74. Klausner RD, Lippincott-Schwartz J, Bonifacino JS. The T cell antigen receptor: insights into organelle biology. Annu Rev Cell Biol 1990;6:403-431.
75. Ono S, Ohno I, Saito T. Rapid turnover of the CD3ζ chain independent of the TCR-CD3 complex in normal cells. Immunity 1995;2:639-644.
76. Finetti F, et al. Intraflagellar transport is required for polarized recycling of the TCR/CD3 complex to the immune synapse. Nat Cell Biol 2009;11:1332-1339.
77. Finetti F, Baldari CT. Compartmentalization of signaling by vesicular trafficking: a shared building design for the immune synapse and the primary cilium. Immunol Rev 2013;251:97-112.
78. Derivery E, Sousa C, Gautier JJ, Lombard B, Loew D, Gautreau A. The Arp2/3 activator WASH controls the fission of endosomes through a large multiprotein complex. Dev Cell 2009;17:712-723.
79. Gomez TS, Billadeau DD. A FAM21-containing WASH complex regulates retromer-dependent sorting. Dev Cell 2009;17:699-711.
80. Piotrowski JT, Gomez TS, Schoon RA, Mangalam AK, Billadeau DD. WASH knockout T cells demonstrate defective receptor trafficking, proliferation, and effector function. Mol Cell Biol 2013;33:958-973.
81. Patino-Lopez G, et al. Rab35 and its GAP EPI64C in T cells regulate receptor recycling and immunological synapse formation. J Biol Chem 2008;283:18323-18330.
82. Springer TA, Dustin ML. Integrin inside-out signaling and the immunological synapse. Curr Opin Cell Biol 2012;24:107-115.
83. Bretscher MS. Aguado-Velasco. Membrane traffic during cell locomotion. Curr Opin Cell Biol 1998;10:537-541.
84. Caswell PT, Vadrevu S, Norman JC. Integrins: masters and slaves of endocytic transport. Nat Rev Mol Cell Biol 2009;10:843-853.
85. Paccani SR, et al. The Bordetella pertussis adenylate cyclase toxin binds to T cells via LFA-1 and induces its disengagement from the immune synapse. J Exp Med 2011;208:1317-1330.
86. Linsley PS, Bradshaw J, Greene J, Peach R, Bennett KL, Mittler RS. Intracellular trafficking of CTLA-4 and focal localization towards sites of TCR engagement. Immunity 1996;4:535-543.
87. Yokosuka T, et al. Spatiotemporal basis of CTLA-4 costimulatory molecule-mediated negative regulation of T cell activation. Immunity 2010;33:326-339.
88. Ehrlich LIR, Ebert PJR, Krummel MF, Weiss A, Davis MM. Dynamics pf p56lck translocation to the T cell immunological synapse following agonist and antagonist stimulation. Immunity 2002;17:809-822.
89. Anton O, et al. An essential role for the MAL protein in targeting Lck to the plasma membrane of human T lymphocytes. J Exp Med 2008;205:3201-3213.
90. Anton OM, Andres-Delgado L, Reglero-Real N, Batista A, Alonso MA. MAL Protein Controls Protein Sorting at the Supramolecular Activation Cluster of Human T Lymphocytes. J Immunol 2011;186:6345-6356.
91. Gorska MM, Liang Q, Karim Z, Alam R. Uncoordinated 119 protein controls trafficking of Lck via the Rab11 endosome and is critical for immunological synapse formation. J Immunol 2009;183:1675-1684.
92. Bonello G, et al. Dynamic recruitment of the adaptor protein LAT: LAT exists in two distinct intracellular pools and controls its own recruitment. J Cell Sci 2004;117:1009-1016.
93. Purbhoo MA, et al. Dynamics of subsynaptic vesicles and surface microclusters at the immunological synapse. Sci Signal 2010;3:ra36.
94. Larghi P, et al. VAMP7 controls T cell activation by regulating the recruitment and phosphorylation of vesicular Lat at TCR-activation sites. Nat Immunol 2013;14:723-731.
95. Balagopalan L, Barr VA, Kortum RL, Park AK, Samelson LE. Cutting edge: cell surface linker for activation of T cells is recruited to microclusters and is active in signaling. J Immunol 2013;190:3849-3853.
96. Sherman E, et al. Functional nanoscale organization of signaling molecules downstream of the T cell antigen receptor. Immunity 2011;35:705-720.
97. Lillemeier BF, Mortelmaier MA, Forstner MB, Huppa JB, Groves JT, Davis MM. TCR and Lat are expressed on separate protein islands on T cell membranes and concatenate during activation. Nat Immunol 2010;11:90-96.
98. Williamson DJ, et al. Pre-existing clusters of the adaptor Lat do not participate in early T cell signaling events. Nat Immunol 2011;12:655-662.
99. Purbhoo MA. The function of sub-synaptic vesicles during T-cell activation. Immunol Rev 2013;251:36-48.
100. Kupfer A, Mosmann TR, Kupfer H. Polarized expression of cytokines in cell conjugates of helper T cells and splenic B cells. Proc Natl Acad Sci USA 1991;88:775-779.
101. Depoil D, et al. Immunological synapses are versatile structures enabling selective T cell polarization. Immunity 2005;22:185-194.
102. Huse M, Lillemeier BF, Kuhns MS, Chen DS, Davis MM. T cells use two directionally distinct pathways for cytokine secretion. Nat Immunol 2006;7:247-255.
103. Bertrand F, et al. Activation of the ancestral polarity regulator protein kinase C zeta at the immunological synapse drives polarization of Th cell secretory machinery toward APCs. J Immunol 2010;185:2887-2894.
104. de Saint Basile G, Menasche G, Fischer A. Molecular mechanisms of biogenesis and exocytosis of cytotoxic granules. Nat Rev Immunol 2010;10:568-579.
105. Angus KL, Griffiths GM. Cell polarisation and the immunological synapse. Curr Opin Cell Biol 2013;25:85-91.
106. Hivroz C, Chemin K, Tourret M, Bohineust A. Crosstalk between T lymphocytes and dendritic cells. Crit Rev Immunol 2012;32:139-155.
107. Griffiths GM, Tsun A, Stinchcombe JC. The immunological synapse: a focal point for endocytosis and exocytosis. J Cell Biol 2010;189:399-406.
108. Stinchcombe JC, Bossi G, Booth S, Griffiths GM. The immunological synapse of CTL contains a secretory domain and membrane bridges. Immunity 2001;15:751-761.
109. Kurowska M, et al. Terminal transport of lytic granules to the immune synapse is mediated by the kinesin-1/Slp3/Rab27a complex. Blood 2012;119:3879-3889.
110. Faroudi M, et al. Lytic versus stimulatory synapse in cytotoxic T lymphocyte/target cell interaction: manifestation of a dual activation threshold. Proc Natl Acad Sci USA 2003;100:14145-14150.
111. Yokosuka T, et al. Newly generated T cell receptor microclusters initiate and sustain T cell activation by recruitment of Zap70 and SLP-76. Nat Immunol 2005;6:1253-1262.
112. Lee KH, Holdorf AD, Dustin ML, Chan AC, Allen P, Shaw AS. T cell receptor signaling precedes immunological synapse formation. Science 2002;295:1539-1542.
113. Varma R, Campi G, Yokosuka T, Saito T, Dustin ML. T cell receptor-proximal signals are sustained in peripheral microclusters and terminated in the central supramolecular activation cluster. Immunity 2006;25:117-127.
114. Balagopalan L, et al. c-Cbl-mediated regulation of LAT-nucleated signaling complexes. Mol Cell Biol 2007;27:8622-8636.
115. Barr VA, et al. T-cell antigen receptor-induced signaling complexes: internalization via a cholesterol-dependent endocytic pathway. Traffic 2006;7:1143-1162.
116. Yokosuka T, Takamatsu M, Kobayashi-Imanishi W, Hashimoto-Tane A, Azuma M, Saito T. Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2. J Exp Med 2012;209:1201-1217.
117. Mossman KD, Campi G, Groves JT, Dustin ML. Altered TCR signaling from geometrically repatterned immunological synapses. Science 2005;310:1191-1193.
118. Nguyen K, Sylvain NR, Bunnell SC. T cell costimulation via the integrin VLA-4 inhibits the actin-dependent centralization of signaling microclusters containing the adaptor SLP-76. Immunity 2008;28:810-821.
119. Hammer JA 3rd, Burkhardt JK. Controversy and consensus regarding myosin II function at the immunological synapse. Curr Opin Immunol 2013;25:300-306.
120. Babich A, Li S, O'Connor RS, Milone MC, Freedman BD, Burkhardt JK. F-actin polymerization and retrograde flow drive sustained PLCgamma1 signaling during T cell activation. J Cell Biol 2012;197:775-787.
121. Vardhana S, Choudhuri K, Varma R, Dustin ML. Essential role of ubiquitin and TSG101 protein in formation and function of the central supramolecular activation cluster. Immunity 2010;32:531-540.
122. Monjas A, Alcover A, Alarcon B. Engaged and bystander T cell receptors are down-modulated by different endocytotic pathways. J Biol Chem 2004;279:55376-55384.
123. Martinez-Martin N, et al. T cell receptor internalization from the immunological synapse is mediated by TC21 and RhoG GTPase-dependent phagocytosis. Immunity 2011;35:208-222.
124. Ahmed KA, Xiang J. Mechanisms of cellular communication through intercellular protein transfer. J Cell Mol Med 2011;15:1458-1473.
125. Balagopalan L, et al. Enhanced T-cell signaling in cells bearing linker for activation of T-cell (LAT) molecules resistant to ubiquitylation. Proc Natl Acad Sci USA 2011;108:2885-2890.
126. Balagopalan L, Barr VA, Samelson LE. Endocytic events in TCR signaling: focus on adapters in microclusters. Immunol Rev 2009;232:84-98.
127. Lasserre R, et al. Release of serine/threonine-phosphorylated adaptors from signaling microclusters down-regulates T cell activation. J Cell Biol 2011;195:839-853.
128. Sadowski L, Pilecka I, Miaczynska M. Signaling from endosomes: location makes a difference. Exp Cell Res 2009;315:1601-1609.
129. Yudushkin IA, Vale RD. Imaging T-cell receptor activation reveals accumulation of tyrosine-phosphorylated CD3zeta in the endosomal compartment. Proc Natl Acad Sci USA 2010;107:22128-22133.
130. Campello S, Lacalle RA, Bettella M, Manes S, Scorrano L, Viola A. Orchestration of lymphocyte chemotaxis by mitochondrial dynamics. J Exp Med 2006;203:2879-2886.
131. Verstreken P, Ly CV, Venken KJ, Koh TW, Zhou Y, Bellen HJ. Synaptic mitochondria are critical for mobilization of reserve pool vesicles at Drosophila neuromuscular junctions. Neuron 2005;47:365-378.
132. Quintana A, Schwarz EC, Schwindling C, Lipp P, Kaestner L, Hoth M. Sustained activity of calcium release-activated calcium channels requires translocation of mitochondria to the plasma membrane. J Biol Chem 2006;281:40302-40309.
133. Quintana A, et al. T cell activation requires mitochondrial translocation to the immunological synapse. Proc Natl Acad Sci USA 2007;104:14418-14423.
134. Baixauli F, et al. The mitochondrial fission factor dynamin-related protein 1 modulates T-cell receptor signalling at the immune synapse. EMBO J 2011;30:1238-1250.
135. Quintana A, et al. Calcium microdomains at the immunological synapse: how ORAI channels, mitochondria and calcium pumps generate local calcium signals for efficient T-cell activation. EMBO J 2011;30:3895-3912.
136. Quintana A, Hoth M. Mitochondrial dynamics and their impact on T cell function. Cell Calcium 2012;52:57-63.
137. Schwindling C, Quintana A, Krause E, Hoth M. Mitochondria positioning controls local calcium influx in T cells. J Immunol 2010;184:184-190.
138. Abraham L, Fackler OT. HIV-1 Nef: a multifaceted modulator of T cell receptor signaling. Cell Commun Signal 2012;10:39.
139. Thoulouze MI, Sol-Foulon N, Blanchet F, Dautry-Varsat A, Schwartz O, Alcover A. Human immunodeficiency virus type-1 infection impairs the formation of the immunological synapse. Immunity 2006;24:547-561.
140. Das SR, Jameel S. Biology of the HIV Nef protein. Indian J Med Res 2005;121:315-332.
141. Fackler OT, Alcover A, Schwartz O. Modulation of the immunological synapse: a key to HIV-1 pathogenesis? Nat Rev Immunol 2007;7:310-317.
142. Schindler M, et al. Nef-mediated suppression of T cell activation was lost in a lentiviral lineage that gave rise to HIV-1. Cell 2006;125:1055-1067.
143. Rudolph JM, Eickel N, Haller C, Schindler M, Fackler OT. Inhibition of T-cell receptor-induced actin remodeling and relocalization of Lck are evolutionarily conserved activities of lentiviral Nef proteins. J Virol 2009;83:11528-11539.
144. Abraham L, Bankhead P, Pan X, Engel U, Fackler OT. HIV-1 Nef Limits Communication between Linker of Activated T Cells and SLP-76 To Reduce Formation of SLP-76-Signaling Microclusters following TCR Stimulation. J Immunol 2012;189:1898-1910.
145. Ott M, et al. Immune hyperactivation of HIV-1-infected T cells mediated by Tat and the CD28 pathway. Science 1997;275:1481-1485.
146. Simmons A, Aluvihare V, McMichael A. Nef triggers a transcriptional program in T cells imitating single-signal T cell activation and inducing HIV virulence mediators. Immunity 2001;14:763-777.
147. Fenard D, Yonemoto W, de Noronha C, Cavrois M, Williams SA, Greene WC. Nef is physically recruited into the immunological synapse and potentiates T cell activation early after TCR engagment. J Immunol 2005;175:6050-6057.
148. Pan X, et al. HIV-1 Nef compensates for disorganization of the immunological synapse by inducing trans-Golgi network-associated Lck signaling. Blood 2012;119:786-797.
149. Haller C, et al. The HIV-1 pathogenicity factor Nef interferes with maturation of stimulatory T-lymphocyte contacts by modulation of N-Wasp activity. J Biol Chem 2006;281:19618-19630.
150. Haller C, Rauch S, Fackler OT. HIV-1 Nef employs two distinct mechanisms to modulate Lck subcellular localization and TCR induced actin remodeling. PLoS ONE 2007;2:e1212.
151. Lehmann M, Nikolic DS, Piguet V. How HIV-1 takes advantage of the cytoskeleton during replication and cell-to-cell transmission. Viruses 2011;3:1757-1776.