Molecular mechanisms and functional implications of polarized actin remodeling at the T cell immunological synapse

Cellular and Molecular Life Sciences

Volumn 72, Issue 3, 2015, Pages 537-556

  Le Floc'H, Audrey ^a   Huse, Morgan ^a  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

Actin; Cytoskeleton; Cytotoxicity; Immunological synapse; Signal transduction; T cell receptor; T cells

Indexed keywords

DOCKING PROTEIN; F ACTIN; INTEGRIN; NUCLEATION PROMOTING FACTOR; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN CDC42; PROTEIN DOCK2; RAC PROTEIN; REGULATOR PROTEIN; RHO GUANINE NUCLEOTIDE BINDING PROTEIN; RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR; T LYMPHOCYTE RECEPTOR; UNCLASSIFIED DRUG; WISKOTT ALDRICH SYNDROME PROTEIN; ACTIN;

ACTIN FILAMENT; ANTIGEN PRESENTING CELL; ARTICLE; CELL ADHESION; CELL INTERACTION; CELL POLARITY; CENTROSOME; CYTOTOXICITY; DEPOLYMERIZATION; ENZYME ACTIVATION; HUMAN; IMMUNOLOGICAL SYNAPSE; LYMPHOCYTE FUNCTION; MICROTUBULE; NONHUMAN; PROTEIN FUNCTION; PROTEIN MODIFICATION; PROTEIN TRANSPORT; SIGNAL TRANSDUCTION; SYNAPTOGENESIS; T LYMPHOCYTE; BIOLOGICAL MODEL; CELL COMMUNICATION; CYTOLOGY; IMMUNOLOGY; METABOLISM;

ACTIN CYTOSKELETON; ACTINS; CELL COMMUNICATION; HUMANS; IMMUNOLOGICAL SYNAPSES; MODELS, IMMUNOLOGICAL; PHOSPHATIDYLINOSITOL 3-KINASES; RHO GTP-BINDING PROTEINS; SIGNAL TRANSDUCTION; T-LYMPHOCYTES;

EID: 84921390271     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-014-1760-7     Document Type: Article

References (186)

1. Dustin ML, Chakraborty AK, Shaw AS (2010) Understanding the structure and function of the immunological synapse. Cold Spring Harb Perspect Biol 2(10):a002311. doi: 10.1101/cshperspect.a002311
2. Harwood NE, Batista FD (2010) Early events in B cell activation. Annu Rev Immunol 28:185-210
3. Dustin ML, Long EO (2010) Cytotoxic immunological synapses. Immunol Rev 235(1):24-34. doi: 10.1111/j.0105-2896.2010.00904.x
4. Gomez TS, Billadeau DD (2008) T cell activation and the cytoskeleton: you can't have one without the other. Adv Immunol 97:1-64
5. Yi J, Wu XS, Crites T, Hammer JA 3rd (2012) Actin retrograde flow and actomyosin II arc contraction drive receptor cluster dynamics at the immunological synapse in Jurkat T cells. Mol Biol Cell 23(5):834-852. doi: 10.1091/mbc.E11-08-0731
6. Brown AC, Oddos S, Dobbie IM, Alakoskela JM, Parton RM, Eissmann P, Neil MA, Dunsby C, French PM, Davis I, Davis DM (2011) Remodelling of cortical actin where lytic granules dock at natural killer cell immune synapses revealed by super-resolution microscopy. PLoS Biol 9(9):e1001152. doi: 10.1371/journal.pbio.1001152
7. Rak GD, Mace EM, Banerjee PP, Svitkina T, Orange JS (2011) Natural killer cell lytic granule secretion occurs through a pervasive actin network at the immune synapse. PLoS Biol 9(9):e1001151. doi: 10.1371/journal.pbio.1001151
8. Stinchcombe JC, Majorovits E, Bossi G, Fuller S, Griffiths GM (2006) Centrosome polarization delivers secretory granules to the immunological synapse. Nature 443(7110):462-465
9. Huse M, Quann EJ, Davis MM (2008) Shouts, whispers, and the kiss of death: directional secretion in T cells. Nat Immunol 9(10):1105-1111
10. Stinchcombe JC, Griffiths GM (2007) Secretory mechanisms in cell-mediated cytotoxicity. Annu Rev Cell Dev Biol 23:495-517
11. Balagopalan L, Sherman E, Barr VA, Samelson LE (2011) Imaging techniques for assaying lymphocyte activation in action. Nat Rev 11(1):21-33. doi: 10.1038/nri2903
12. Groves JT, Dustin ML (2003) Supported planar bilayers in studies on immune cell adhesion and communication. J Immunol Methods 278(1-2):19-32
13. Schneckenburger H (2005) Total internal reflection fluorescence microscopy: technical innovations and novel applications. Curr Opin Biotechnol 16(1):13-18
14. Sherman E, Barr V, Manley S, Patterson G, Balagopalan L, Akpan I, Regan CK, Merrill RK, Sommers CL, Lippincott-Schwartz J, Samelson LE (2011) Functional nanoscale organization of signaling molecules downstream of the T cell antigen receptor. Immunity 35(5):705-720. doi: 10.1016/j.immuni.2011.10.004
15. Williamson DJ, Owen DM, Rossy J, Magenau A, Wehrmann M, Gooding JJ, Gaus K (2011) Pre-existing clusters of the adaptor Lat do not participate in early T cell signaling events. Nat Immunol 12(7):655-662. doi: 10.1038/ni.2049
16. Lillemeier BF, Mortelmaier MA, Forstner MB, Huppa JB, Groves JT, Davis MM (2009) TCR and Lat are expressed on separate protein islands on T cell membranes and concatenate during activation. Nat Immunol 11(1):90-96
17. Huse M, Klein LO, Girvin AT, Faraj JM, Li QJ, Kuhns MS, Davis MM (2007) Spatial and temporal dynamics of T cell receptor signaling with a photoactivatable agonist. Immunity 27(1):76-88
18. Stinchcombe JC, Bossi G, Booth S, Griffiths GM (2001) The immunological synapse of CTL contains a secretory domain and membrane bridges. Immunity 15(5):751-761
19. + T-cell synapses involve multiple distinct stages. Proc Natl Acad Sci USA 108(41):17099-17104. doi: 10.1073/pnas.1113703108
20. Boes M, Cerny J, Massol R, Op den Brouw M, Kirchhausen T, Chen J, Ploegh HL (2002) T-cell engagement of dendritic cells rapidly rearranges MHC class II transport. Nature 418(6901):983-988. doi: 10.1038/nature01004
21. Chow A, Toomre D, Garrett W, Mellman I (2002) Dendritic cell maturation triggers retrograde MHC class II transport from lysosomes to the plasma membrane. Nature 418(6901):988-994. doi: 10.1038/nature01006
22. Pulecio J, Petrovic J, Prete F, Chiaruttini G, Lennon-Dumenil AM, Desdouets C, Gasman S, Burrone OR, Benvenuti F (2010) Cdc42-mediated MTOC polarization in dendritic cells controls targeted delivery of cytokines at the immune synapse. J Exp Med 207(12):2719-2732. doi: 10.1084/jem.20100007
23. Huse M (2009) The T-cell-receptor signaling network. J Cell Sci 122(Pt 9):1269-1273
24. Derivery E, Gautreau A (2010) Generation of branched actin networks: assembly and regulation of the N-WASP and WAVE molecular machines. BioEssays 32(2):119-131. doi: 10.1002/bies.200900123
25. Goley ED, Welch MD (2006) The ARP2/3 complex: an actin nucleator comes of age. Nat Rev Mol Cell Biol 7(10):713-726. doi: 10.1038/nrm2026
26. Gomez TS, Kumar K, Medeiros RB, Shimizu Y, Leibson PJ, Billadeau DD (2007) Formins regulate the actin-related protein 2/3 complex-independent polarization of the centrosome to the immunological synapse. Immunity 26(2):177-190
27. Jaffe AB, Hall A (2005) Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol 21:247-269
28. Ramesh N, Geha R (2009) Recent advances in the biology of WASP and WIP. Immunol Res 44(1-3):99-111. doi: 10.1007/s12026-008-8086-1
29. Ku GM, Yablonski D, Manser E, Lim L, Weiss A (2001) A PAK1-PIX-PKL complex is activated by the T-cell receptor independent of Nck, Slp-76 and LAT. EMBO J 20(3):457-465. doi: 10.1093/emboj/20.3.457
30. Sanui T, Inayoshi A, Noda M, Iwata E, Oike M, Sasazuki T, Fukui Y (2003) DOCK2 is essential for antigen-induced translocation of TCR and lipid rafts, but not PKC-theta and LFA-1. T cells. Immunity 19(1):119-129
31. Cannon JL, Labno CM, Bosco G, Seth A, McGavin MH, Siminovitch KA, Rosen MK, Burkhardt JK (2001) Wasp recruitment to the T cell:APC contact site occurs independently of Cdc42 activation. Immunity 15(2):249-259
32. Higgs HN, Pollard TD (2000) Activation by Cdc42 and PIP(2) of Wiskott-Aldrich syndrome protein (WASp) stimulates actin nucleation by Arp2/3 complex. J Cell Biol 150(6):1311-1320
33. Rohatgi R, Ma L, Miki H, Lopez M, Kirchhausen T, Takenawa T, Kirschner MW (1999) The interaction between N-WASP and the Arp2/3 complex links Cdc42-dependent signals to actin assembly. Cell 97(2):221-231
34. Ochs HD (1998) The Wiskott-Aldrich syndrome. Semin Hematol 35(4):332-345
35. Molina IJ, Sancho J, Terhorst C, Rosen FS, Remold-O'Donnell E (1993) T cells of patients with the Wiskott-Aldrich syndrome have a restricted defect in proliferative responses. J Immunol 151(8):4383-4390
36. + T cells from Wiskott-Aldrich syndrome patients. J Immunol 177(10):7451-7461
37. Barda-Saad M, Shirasu N, Pauker MH, Hassan N, Perl O, Balbo A, Yamaguchi H, Houtman JC, Appella E, Schuck P, Samelson LE (2010) Cooperative interactions at the SLP-76 complex are critical for actin polymerization. EMBO J 29(14):2315-2328. doi: 10.1038/emboj.2010.133
38. Tybulewicz VL (2005) Vav-family proteins in T-cell signalling. Curr Opin Immunol 17(3):267-274
39. Zhang J, Shehabeldin A, da Cruz LA, Butler J, Somani AK, McGavin M, Kozieradzki I, dos Santos AO, Nagy A, Grinstein S, Penninger JM, Siminovitch KA (1999) Antigen receptor-induced activation and cytoskeletal rearrangement are impaired in Wiskott-Aldrich syndrome protein-deficient lymphocytes. J Exp Med 190(9):1329-1342
40. Gallego MD, Santamaria M, Pena J, Molina IJ (1997) Defective actin reorganization and polymerization of Wiskott-Aldrich T cells in response to CD3-mediated stimulation. Blood 90(8):3089-3097
41. Calvez R, Lafouresse F, De Meester J, Galy A, Valitutti S, Dupre L (2011) The Wiskott-Aldrich syndrome protein permits assembly of a focused immunological synapse enabling sustained T-cell receptor signaling. Haematologica 96(10):1415-1423. doi: 10.3324/haematol.2011.040204
42. Kenney D, Cairns L, Remold-O'Donnell E, Peterson J, Rosen FS, Parkman R (1986) Morphological abnormalities in the lymphocytes of patients with the Wiskott-Aldrich syndrome. Blood 68(6):1329-1332
43. Cannon JL, Burkhardt JK (2004) Differential roles for Wiskott-Aldrich syndrome protein in immune synapse formation and IL-2 production. J Immunol 173(3):1658-1662
44. Krawczyk C, Oliveira-dos-Santos A, Sasaki T, Griffiths E, Ohashi PS, Snapper S, Alt F, Penninger JM (2002) Vav1 controls integrin clustering and MHC/peptide-specific cell adhesion to antigen-presenting cells. Immunity 16(3):331-343
45. Sims TN, Soos TJ, Xenias HS, Dubin-Thaler B, Hofman JM, Waite JC, Cameron TO, Thomas VK, Varma R, Wiggins CH, Sheetz MP, Littman DR, Dustin ML (2007) Opposing effects of PKCtheta and WASp on symmetry breaking and relocation of the immunological synapse. Cell 129(4):773-785
46. + T cells at the immunological synapse requires Cdc42-dependent local actin remodeling but not microtubule organizing center polarity. J Immunol 189(5):2159-2168. doi: 10.4049/jimmunol.1200156
47. Dustin ML (2007) Cell adhesion molecules and actin cytoskeleton at immune synapses and kinapses. Curr Opin Cell Biol 19(5):529-533. doi: 10.1016/j.ceb.2007.08.003
48. Nolz JC, Gomez TS, Zhu P, Li S, Medeiros RB, Shimizu Y, Burkhardt JK, Freedman BD, Billadeau DD (2006) The WAVE2 complex regulates actin cytoskeletal reorganization and CRAC-mediated calcium entry during T cell activation. Curr Biol 16(1):24-34
49. Le Floc'h A, Tanaka Y, Bantilan NS, Voisinne G, Altan-Bonnet G, Fukui Y, Huse M (2013) Annular PIP3 accumulation controls actin architecture and modulates cytotoxicity at the immunological synapse. J Exp Med 210(12):2721-2737. doi: 10.1084/jem.20131324
50. Yu H, Leitenberg D, Li B, Flavell RA (2001) Deficiency of small GTPase Rac2 affects T cell activation. J Exp Med 194(7):915-926
51. de la Roche M, Ritter AT, Angus KL, Dinsmore C, Earnshaw CH, Reiter JF, Griffiths GM (2013) Hedgehog signaling controls T cell killing at the immunological synapse. Science 342(6163):1247-1250. doi: 10.1126/science.1244689
52. Hao JJ, Zhu J, Zhou K, Smith N, Zhan X (2005) The coiled-coil domain is required for HS1 to bind to F-actin and activate Arp2/3 complex. J Biol Chem 280(45):37988-37994. doi: 10.1074/jbc.M504552200
53. Gomez TS, McCarney SD, Carrizosa E, Labno CM, Comiskey EO, Nolz JC, Zhu P, Freedman BD, Clark MR, Rawlings DJ, Billadeau DD, Burkhardt JK (2006) HS1 functions as an essential actin-regulatory adaptor protein at the immune synapse. Immunity 24(6):741-752
54. Carrizosa E, Gomez TS, Labno CM, Klos Dehring DA, Liu X, Freedman BD, Billadeau DD, Burkhardt JK (2009) Hematopoietic lineage cell-specific protein 1 is recruited to the immunological synapse by IL-2-inducible T cell kinase and regulates phospholipase Cgamma1 Microcluster dynamics during T cell spreading. J Immunol 183(11):7352-7361. doi: 10.4049/jimmunol.0900973
55. Dehring DA, Clarke F, Ricart BG, Huang Y, Gomez TS, Williamson EK, Hammer DA, Billadeau DD, Argon Y, Burkhardt JK (2011) Hematopoietic lineage cell-specific protein 1 functions in concert with the Wiskott-Aldrich syndrome protein to promote podosome array organization and chemotaxis in dendritic cells. J Immunol 186(8):4805-4818. doi: 10.4049/jimmunol.1003102
56. Rossman KL, Der CJ, Sondek J (2005) GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors. Nat Rev Mol Cell Biol 6(2):167-180. doi: 10.1038/nrm1587
57. Zeng R, Cannon JL, Abraham RT, Way M, Billadeau DD, Bubeck-Wardenberg J, Burkhardt JK (2003) SLP-76 coordinates Nck-dependent Wiskott-Aldrich syndrome protein recruitment with Vav-1/Cdc42-dependent Wiskott-Aldrich syndrome protein activation at the T cell-APC contact site. J Immunol 171(3):1360-1368
58. Ardouin L, Bracke M, Mathiot A, Pagakis SN, Norton T, Hogg N, Tybulewicz VL (2003) Vav1 transduces TCR signals required for LFA-1 function and cell polarization at the immunological synapse. Eur J Immunol 33(3):790-797
59. Fischer KD, Kong YY, Nishina H, Tedford K, Marengere LE, Kozieradzki I, Sasaki T, Starr M, Chan G, Gardener S, Nghiem MP, Bouchard D, Barbacid M, Bernstein A, Penninger JM (1998) Vav is a regulator of cytoskeletal reorganization mediated by the T-cell receptor. Curr Biol 8(10):554-562
60. Holsinger LJ, Graef IA, Swat W, Chi T, Bautista DM, Davidson L, Lewis RS, Alt FW, Crabtree GR (1998) Defects in actin-cap formation in Vav-deficient mice implicate an actin requirement for lymphocyte signal transduction. Curr Biol 8(10):563-572
61. Wulfing C, Bauch A, Crabtree GR, Davis MM (2000) The vav exchange factor is an essential regulator in actin-dependent receptor translocation to the lymphocyte-antigen-presenting cell interface. Proc Natl Acad Sci USA 97(18):10150-10155
62. Reynolds LF, de Bettignies C, Norton T, Beeser A, Chernoff J, Tybulewicz VL (2004) Vav1 transduces T cell receptor signals to the activation of the Ras/ERK pathway via LAT, Sos, and RasGRP1. J Biol Chem 279(18):18239-18246. doi: 10.1074/jbc.M400257200
63. Reynolds LF, Smyth LA, Norton T, Freshney N, Downward J, Kioussis D, Tybulewicz VL (2002) Vav1 transduces T cell receptor signals to the activation of phospholipase C-gamma1 via phosphoinositide 3-kinase-dependent and -independent pathways. J Exp Med 195(9):1103-1114
64. Faure S, Salazar-Fontana LI, Semichon M, Tybulewicz VL, Bismuth G, Trautmann A, Germain RN, Delon J (2004) ERM proteins regulate cytoskeleton relaxation promoting T cell-APC conjugation. Nat Immunol 5(3):272-279. doi: 10.1038/ni1039
65. Bretscher A, Edwards K, Fehon RG (2002) ERM proteins and merlin: integrators at the cell cortex. Nat Rev Mol Cell Biol 3(8):586-599. doi: 10.1038/nrm882
66. Miletic AV, Graham DB, Sakata-Sogawa K, Hiroshima M, Hamann MJ, Cemerski S, Kloeppel T, Billadeau DD, Kanagawa O, Tokunaga M, Swat W (2009) Vav links the T cell antigen receptor to the actin cytoskeleton and T cell activation independently of intrinsic Guanine nucleotide exchange activity. PLoS ONE 4(8):e6599. doi: 10.1371/journal.pone.0006599
67. Cote JF, Vuori K (2007) GEF what? Dock180 and related proteins help Rac to polarize cells in new ways. Trends Cell Biol 17(8):383-393. doi: 10.1016/j.tcb.2007.05.001
68. Nishikimi A, Kukimoto-Niino M, Yokoyama S, Fukui Y (2013) Immune regulatory functions of DOCK family proteins in health and disease. Exp Cell Res 319(15):2343-2349. doi: 10.1016/j.yexcr.2013.07.024
69. Kunisaki Y, Nishikimi A, Tanaka Y, Takii R, Noda M, Inayoshi A, Watanabe K, Sanematsu F, Sasazuki T, Sasaki T, Fukui Y (2006) DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis. J Cell Biol 174(5):647-652. doi: 10.1083/jcb.200602142
70. Nishikimi A, Fukuhara H, Su W, Hongu T, Takasuga S, Mihara H, Cao Q, Sanematsu F, Kanai M, Hasegawa H, Tanaka Y, Shibasaki M, Kanaho Y, Sasaki T, Frohman MA, Fukui Y (2009) Sequential regulation of DOCK2 dynamics by two phospholipids during neutrophil chemotaxis. Science 324(5925):384-387. doi: 10.1126/science.1170179
71. Fukui Y, Hashimoto O, Sanui T, Oono T, Koga H, Abe M, Inayoshi A, Noda M, Oike M, Shirai T, Sasazuki T (2001) Haematopoietic cell-specific CDM family protein DOCK2 is essential for lymphocyte migration. Nature 412(6849):826-831. doi: 10.1038/35090591
72. Nombela-Arrieta C, Lacalle RA, Montoya MC, Kunisaki Y, Megias D, Marques M, Carrera AC, Manes S, Fukui Y, Martinez AC, Stein JV (2004) Differential requirements for DOCK2 and phosphoinositide-3-kinase gamma during T and B lymphocyte homing. Immunity 21(3):429-441. doi: 10.1016/j.immuni.2004.07.012
73. Ham H, Guerrier S, Kim J, Schoon RA, Anderson EL, Hamann MJ, Lou Z, Billadeau DD (2013) Dedicator of cytokinesis 8 interacts with talin and Wiskott-Aldrich syndrome protein to regulate NK cell cytotoxicity. J Immunol 190(7):3661-3669. doi: 10.4049/jimmunol.1202792
74. Randall KL, Chan SS, Ma CS, Fung I, Mei Y, Yabas M, Tan A, Arkwright PD, Al Suwairi W, Lugo Reyes SO, Yamazaki-Nakashimada MA, Garcia-Cruz Mde L, Smart JM, Picard C, Okada S, Jouanguy E, Casanova JL, Lambe T, Cornall RJ, Russell S, Oliaro J, Tangye SG, Bertram EM, Goodnow CC (2011) DOCK8 deficiency impairs CD8 T cell survival and function in humans and mice. J Exp Med 208(11):2305-2320. doi: 10.1084/jem.20110345
75. Randall KL, Lambe T, Goodnow CC, Cornall RJ (2010) The essential role of DOCK8 in humoral immunity. Dis Markers 29(3-4):141-150. doi: 10.3233/DMA-2010-0739
76. Randall KL, Lambe T, Johnson AL, Treanor B, Kucharska E, Domaschenz H, Whittle B, Tze LE, Enders A, Crockford TL, Bouriez-Jones T, Alston D, Cyster JG, Lenardo MJ, Mackay F, Deenick EK, Tangye SG, Chan TD, Camidge T, Brink R, Vinuesa CG, Batista FD, Cornall RJ, Goodnow CC (2009) Dock8 mutations cripple B cell immunological synapses, germinal centers and long-lived antibody production. Nat Immunol 10(12):1283-1291. doi: 10.1038/ni.1820
77. Engelhardt KR, McGhee S, Winkler S, Sassi A, Woellner C, Lopez-Herrera G, Chen A, Kim HS, Lloret MG, Schulze I, Ehl S, Thiel J, Pfeifer D, Veelken H, Niehues T, Siepermann K, Weinspach S, Reisli I, Keles S, Genel F, Kutukculer N, Camcioglu Y, Somer A, Karakoc-Aydiner E, Barlan I, Gennery A, Metin A, Degerliyurt A, Pietrogrande MC, Yeganeh M, Baz Z, Al-Tamemi S, Klein C, Puck JM, Holland SM, McCabe ER, Grimbacher B, Chatila TA (2009) Large deletions and point mutations involving the dedicator of cytokinesis 8 (DOCK8) in the autosomal-recessive form of hyper-IgE syndrome. J Allergy Clin Immunol 124(6):1289-1302. doi: 10.1016/j.jaci.2009.10.038
78. Zhang Q, Davis JC, Lamborn IT, Freeman AF, Jing H, Favreau AJ, Matthews HF, Davis J, Turner ML, Uzel G, Holland SM, Su HC (2009) Combined immunodeficiency associated with DOCK8 mutations. N Engl J Med 361(21):2046-2055. doi: 10.1056/NEJMoa0905506
79. Chang JT, Palanivel VR, Kinjyo I, Schambach F, Intlekofer AM, Banerjee A, Longworth SA, Vinup KE, Mrass P, Oliaro J, Killeen N, Orange JS, Russell SM, Weninger W, Reiner SL (2007) Asymmetric T lymphocyte division in the initiation of adaptive immune responses. Science 315(5819):1687-1691
80. Thaunat O, Granja AG, Barral P, Filby A, Montaner B, Collinson L, Martinez-Martin N, Harwood NE, Bruckbauer A, Batista FD (2012) Asymmetric segregation of polarized antigen on B cell division shapes presentation capacity. Science 335(6067):475-479. doi: 10.1126/science.1214100
81. + memory versus effector development. Science 323(5913):502-505. doi: 10.1126/science.1163612
82. Jabara HH, McDonald DR, Janssen E, Massaad MJ, Ramesh N, Borzutzky A, Rauter I, Benson H, Schneider L, Baxi S, Recher M, Notarangelo LD, Wakim R, Dbaibo G, Dasouki M, Al-Herz W, Barlan I, Baris S, Kutukculer N, Ochs HD, Plebani A, Kanariou M, Lefranc G, Reisli I, Fitzgerald KA, Golenbock D, Manis J, Keles S, Ceja R, Chatila TA, Geha RS (2012) DOCK8 functions as an adaptor that links TLR-MyD88 signaling to B cell activation. Nat Immunol 13(6):612-620. doi: 10.1038/ni.2305
83. Sakai Y, Tanaka Y, Yanagihara T, Watanabe M, Duan X, Terasawa M, Nishikimi A, Sanematsu F, Fukui Y (2013) The Rac activator DOCK2 regulates natural killer cell-mediated cytotoxicity in mice through the lytic synapse formation. Blood 122(3):386-393. doi: 10.1182/blood-2012-12-475897
84. Costello PS, Gallagher M, Cantrell DA (2002) Sustained and dynamic inositol lipid metabolism inside and outside the immunological synapse. Nat Immunol 3(11):1082-1089. doi: 10.1038/ni848
85. Garcon F, Patton DT, Emery JL, Hirsch E, Rottapel R, Sasaki T, Okkenhaug K (2008) CD28 provides T-cell costimulation and enhances PI3K activity at the immune synapse independently of its capacity to interact with the p85/p110 heterodimer. Blood 111(3):1464-1471. doi: 10.1182/blood-2007-08-108050
86. Harriague J, Bismuth G (2002) Imaging antigen-induced PI3K activation in T cells. Nat Immunol 3(11):1090-1096
87. Huppa JB, Gleimer M, Sumen C, Davis MM (2003) Continuous T cell receptor signaling required for synapse maintenance and full effector potential. Nat Immunol 4(8):749-755
88. Fruman DA, Bismuth G (2009) Fine tuning the immune response with PI3 K. Immunol Rev 228(1):253-272. doi: 10.1111/j.1600-065X.2008.00750.x
89. Kok K, Nock GE, Verrall EA, Mitchell MP, Hommes DW, Peppelenbosch MP, Vanhaesebroeck B (2009) Regulation of p110delta PI 3-kinase gene expression. PLoS ONE 4(4):e5145. doi: 10.1371/journal.pone.0005145
90. Okkenhaug K, Ali K, Vanhaesebroeck B (2007) Antigen receptor signalling: a distinctive role for the p110delta isoform of PI3K. Trends Immunol 28(2):80-87
91. Okkenhaug K, Bilancio A, Farjot G, Priddle H, Sancho S, Peskett E, Pearce W, Meek SE, Salpekar A, Waterfield MD, Smith AJ, Vanhaesebroeck B (2002) Impaired B and T cell antigen receptor signaling in p110delta PI 3-kinase mutant mice. Science 297(5583):1031-1034. doi: 10.1126/science.10735601073560
92. Okkenhaug K, Patton DT, Bilancio A, Garcon F, Rowan WC, Vanhaesebroeck B (2006) The p110delta isoform of phosphoinositide 3-kinase controls clonal expansion and differentiation of Th cells. J Immunol 177(8):5122-5128
93. Alcazar I, Marques M, Kumar A, Hirsch E, Wymann M, Carrera AC, Barber DF (2007) Phosphoinositide 3-kinase gamma participates in T cell receptor-induced T cell activation. J Exp Med 204(12):2977-2987. doi: 10.1084/jem.20070366
94. Sauer S, Bruno L, Hertweck A, Finlay D, Leleu M, Spivakov M, Knight ZA, Cobb BS, Cantrell D, O'Connor E, Shokat KM, Fisher AG, Merkenschlager M (2008) T cell receptor signaling controls Foxp3 expression via PI3K, Akt, and mTOR. Proc Natl Acad Sci USA 105(22):7797-7802. doi: 10.1073/pnas.0800928105
95. Funamoto S, Meili R, Lee S, Parry L, Firtel RA (2002) Spatial and temporal regulation of 3-phosphoinositides by PI 3-kinase and PTEN mediates chemotaxis. Cell 109(5):611-623
96. Iijima M, Devreotes P (2002) Tumor suppressor PTEN mediates sensing of chemoattractant gradients. Cell 109(5):599-610
97. Wang F, Herzmark P, Weiner OD, Srinivasan S, Servant G, Bourne HR (2002) Lipid products of PI(3)Ks maintain persistent cell polarity and directed motility in neutrophils. Nat Cell Biol 4(7):513-518. doi: 10.1038/ncb810
98. Molon B, Gri G, Bettella M, Gomez-Mouton C, Lanzavecchia A, Martinez AC, Manes S, Viola A (2005) T cell costimulation by chemokine receptors. Nat Immunol 6(5):465-471. doi: 10.1038/ni1191
99. Bromley SK, Peterson DA, Gunn MD, Dustin ML (2000) Cutting edge: hierarchy of chemokine receptor and TCR signals regulating T cell migration and proliferation. J Immunol 165(1):15-19
100. Saito T, Yokosuka T (2006) Immunological synapse and microclusters: the site for recognition and activation of T cells. Curr Opin Immunol 18(3):305-313
101. Varma R, Campi G, Yokosuka T, Saito T, Dustin ML (2006) T cell receptor-proximal signals are sustained in peripheral microclusters and terminated in the central supramolecular activation cluster. Immunity 25(1):117-127
102. Shim EK, Jung SH, Lee JR (2011) Role of two adaptor molecules SLP-76 and LAT in the PI3K signaling pathway in activated T cells. J Immunol 186(5):2926-2935. doi: 10.4049/jimmunol.1001785
103. Shim EK, Moon CS, Lee GY, Ha YJ, Chae SK, Lee JR (2004) Association of the Src homology 2 domain-containing leukocyte phosphoprotein of 76 kD (SLP-76) with the p85 subunit of phosphoinositide 3-kinase. FEBS Lett 575(1-3):35-40. doi: 10.1016/j.febslet.2004.07.090
104. Zhang W, Sloan-Lancaster J, Kitchen J, Trible RP, Samelson LE (1998) LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation. Cell 92(1):83-92
105. Carpenter CL, Auger KR, Chanudhuri M, Yoakim M, Schaffhausen B, Shoelson S, Cantley LC (1993) Phosphoinositide 3-kinase is activated by phosphopeptides that bind to the SH2 domains of the 85-kDa subunit. J Biol Chem 268(13):9478-9483
106. Holt KH, Olson L, Moye-Rowley WS, Pessin JE (1994) Phosphatidylinositol 3-kinase activation is mediated by high-affinity interactions between distinct domains within the p110 and p85 subunits. Mol Cell Biol 14(1):42-49
107. Rodriguez-Viciana P, Warne PH, Dhand R, Vanhaesebroeck B, Gout I, Fry MJ, Waterfield MD, Downward J (1994) Phosphatidylinositol-3-OH kinase as a direct target of Ras. Nature 370(6490):527-532
108. Rodriguez-Viciana P, Warne PH, Vanhaesebroeck B, Waterfield MD, Downward J (1996) Activation of phosphoinositide 3-kinase by interaction with Ras and by point mutation. EMBO J 15(10):2442-2451
109. Jimenez C, Hernandez C, Pimentel B, Carrera AC (2002) The p85 regulatory subunit controls sequential activation of phosphoinositide 3-kinase by Tyr kinases and Ras. J Biol Chem 277(44):41556-41562. doi: 10.1074/jbc.M205893200
110. Gupta S, Ramjaun AR, Haiko P, Wang Y, Warne PH, Nicke B, Nye E, Stamp G, Alitalo K, Downward J (2007) Binding of ras to phosphoinositide 3-kinase p110alpha is required for ras-driven tumorigenesis in mice. Cell 129(5):957-968. doi: 10.1016/j.cell.2007.03.051
111. Suire S, Condliffe AM, Ferguson GJ, Ellson CD, Guillou H, Davidson K, Welch H, Coadwell J, Turner M, Chilvers ER, Hawkins PT, Stephens L (2006) Gbetagammas and the Ras binding domain of p110gamma are both important regulators of PI(3)Kgamma signalling in neutrophils. Nat Cell Biol 8(11):1303-1309. doi: 10.1038/ncb1494
112. Mor A, Philips MR (2006) Compartmentalized Ras/MAPK signaling. Annu Rev Immunol 24:771-800. doi: 10.1146/annurev.immunol.24.021605.090723
113. Genot E, Cantrell DA (2000) Ras regulation and function in lymphocytes. Curr Opin Immunol 12(3):289-294
114. Mor A, Campi G, Du G, Zheng Y, Foster DA, Dustin ML, Philips MR (2007) The lymphocyte function-associated antigen-1 receptor costimulates plasma membrane Ras via phospholipase D2. Nat Cell Biol 9(6):713-719
115. Jun JE, Rubio I, Roose JP (2013) Regulation of Ras exchange factors and cellular localization of Ras activation by lipid messengers in T cells. Front Immunol 4:239. doi: 10.3389/fimmu.2013.00239
116. Samstag Y, Bader A, Meuer SC (1991) A serine phosphatase is involved in CD2-mediated activation of human T lymphocytes and natural killer cells. J Immunol 147(3):788-794
117. Samstag Y, Eckerskorn C, Wesselborg S, Henning S, Wallich R, Meuer SC (1994) Costimulatory signals for human T-cell activation induce nuclear translocation of pp19/cofilin. Proc Natl Acad Sci USA 91(10):4494-4498
118. Agnew BJ, Minamide LS, Bamburg JR (1995) Reactivation of phosphorylated actin depolymerizing factor and identification of the regulatory site. J Biol Chem 270(29):17582-17587
119. Moriyama K, Iida K, Yahara I (1996) Phosphorylation of Ser-3 of cofilin regulates its essential function on actin. Genes Cells 1(1):73-86
120. Samstag Y, John I, Wabnitz GH (2013) Cofilin: a redox sensitive mediator of actin dynamics during T-cell activation and migration. Immunol Rev 256(1):30-47. doi: 10.1111/imr.12115
121. Eibert SM, Lee KH, Pipkorn R, Sester U, Wabnitz GH, Giese T, Meuer SC, Samstag Y (2004) Cofilin peptide homologs interfere with immunological synapse formation and T cell activation. Proc Natl Acad Sci USA 101(7):1957-1962. doi: 10.1073/pnas.0308282100
122. Freeman SA, Lei V, Dang-Lawson M, Mizuno K, Roskelley CD, Gold MR (2011) Cofilin-mediated F-actin severing is regulated by the Rap GTPase and controls the cytoskeletal dynamics that drive lymphocyte spreading and BCR microcluster formation. J Immunol 187(11):5887-5900. doi: 10.4049/jimmunol.1102233
123. Wabnitz GH, Nebl G, Klemke M, Schroder AJ, Samstag Y (2006) Phosphatidylinositol 3-kinase functions as a Ras effector in the signaling cascade that regulates dephosphorylation of the actin-remodeling protein cofilin after costimulation of untransformed human T lymphocytes. J Immunol 176(3):1668-1674
124. Brieher WM, Kueh HY, Ballif BA, Mitchison TJ (2006) Rapid actin monomer-insensitive depolymerization of Listeria actin comet tails by cofilin, coronin, and Aip1. J Cell Biol 175(2):315-324. doi: 10.1083/jcb.200603149
125. Humphries CL, Balcer HI, D'Agostino JL, Winsor B, Drubin DG, Barnes G, Andrews BJ, Goode BL (2002) Direct regulation of Arp2/3 complex activity and function by the actin binding protein coronin. J Cell Biol 159(6):993-1004. doi: 10.1083/jcb.200206113
126. Kueh HY, Charras GT, Mitchison TJ, Brieher WM (2008) Actin disassembly by cofilin, coronin, and Aip1 occurs in bursts and is inhibited by barbed-end cappers. J Cell Biol 182(2):341-353. doi: 10.1083/jcb.200801027
127. Moshous D, Martin E, Carpentier W, Lim A, Callebaut I, Canioni D, Hauck F, Majewski J, Schwartzentruber J, Nitschke P, Sirvent N, Frange P, Picard C, Blanche S, Revy P, Fischer A, Latour S, Jabado N, de Villartay JP (2013) Whole-exome sequencing identifies Coronin-1A deficiency in 3 siblings with immunodeficiency and EBV-associated B-cell lymphoproliferation. J Allergy Clin Immunol 131(6):1594-1603. doi: 10.1016/j.jaci.2013.01.042
128. Shiow LR, Paris K, Akana MC, Cyster JG, Sorensen RU, Puck JM (2009) Severe combined immunodeficiency (SCID) and attention deficit hyperactivity disorder (ADHD) associated with a Coronin-1A mutation and a chromosome 16p11.2 deletion. Clin Immunol 131(1):24-30. doi: 10.1016/j.clim.2008.11.002
129. Shiow LR, Roadcap DW, Paris K, Watson SR, Grigorova IL, Lebet T, An J, Xu Y, Jenne CN, Foger N, Sorensen RU, Goodnow CC, Bear JE, Puck JM, Cyster JG (2008) The actin regulator coronin 1A is mutant in a thymic egress-deficient mouse strain and in a patient with severe combined immunodeficiency. Nat Immunol 9(11):1307-1315. doi: 10.1038/ni.1662
130. Foger N, Rangell L, Danilenko DM, Chan AC (2006) Requirement for coronin 1 in T lymphocyte trafficking and cellular homeostasis. Science 313(5788):839-842. doi: 10.1126/science.1130563
131. Mueller P, Liu X, Pieters J (2011) Migration and homeostasis of naive T cells depends on coronin 1-mediated prosurvival signals and not on coronin 1-dependent filamentous actin modulation. J Immunol 186(7):4039-4050. doi: 10.4049/jimmunol.1003352
132. Mueller P, Massner J, Jayachandran R, Combaluzier B, Albrecht I, Gatfield J, Blum C, Ceredig R, Rodewald HR, Rolink AG, Pieters J (2008) 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 9(4):424-431. doi: 10.1038/ni1570
133. Mugnier B, Nal B, Verthuy C, Boyer C, Lam D, Chasson L, Nieoullon V, Chazal G, Guo XJ, He HT, Rueff-Juy D, Alcover A, Ferrier P (2008) Coronin-1A links cytoskeleton dynamics to TCR alpha beta-induced cell signaling. PLoS ONE 3(10):e3467. doi: 10.1371/journal.pone.0003467
134. Mace EM, Orange JS (2014) Lytic immune synapse function requires filamentous actin deconstruction by Coronin 1A. Proc Natl Acad Sci USA 111(18):6708-6713. doi: 10.1073/pnas.1314975111
135. Wabnitz GH, Lohneis P, Kirchgessner H, Jahraus B, Gottwald S, Konstandin M, Klemke M, Samstag Y (2010) Sustained LFA-1 cluster formation in the immune synapse requires the combined activities of L-plastin and calmodulin. Eur J Immunol 40(9):2437-2449. doi: 10.1002/eji.201040345
136. Wang C, Morley SC, Donermeyer D, Peng I, Lee WP, Devoss J, Danilenko DM, Lin Z, Zhang J, Zhou J, Allen PM, Brown EJ (2010) Actin-bundling protein L-plastin regulates T cell activation. J Immunol 185(12):7487-7497. doi: 10.4049/jimmunol.1001424
137. Morley SC (2013) The actin-bundling protein L-plastin supports T-cell motility and activation. Immunol Rev 256(1):48-62. doi: 10.1111/imr.12102
138. Le Goff E, Vallentin A, Harmand PO, Aldrian-Herrada G, Rebiere B, Roy C, Benyamin Y, Lebart MC (2010) Characterization of L-plastin interaction with beta integrin and its regulation by micro-calpain. Cytoskeleton 67(5):286-296. doi: 10.1002/cm.20442
139. Janji B, Giganti A, De Corte V, Catillon M, Bruyneel E, Lentz D, Plastino J, Gettemans J, Friederich E (2006) Phosphorylation on Ser5 increases the F-actin-binding activity of L-plastin and promotes its targeting to sites of actin assembly in cells. J Cell Sci 119(Pt 9):1947-1960. doi: 10.1242/jcs.02874
140. Gardel ML, Schneider IC, Aratyn-Schaus Y, Waterman CM (2010) Mechanical integration of actin and adhesion dynamics in cell migration. Annu Rev Cell Dev Biol 26:315-333. doi: 10.1146/annurev.cellbio.011209.122036
141. Wilson CA, Tsuchida MA, Allen GM, Barnhart EL, Applegate KT, Yam PT, Ji L, Keren K, Danuser G, Theriot JA (2010) Myosin II contributes to cell-scale actin network treadmilling through network disassembly. Nature 465(7296):373-377. doi: 10.1038/nature08994
142. Ilani T, Vasiliver-Shamis G, Vardhana S, Bretscher A, Dustin ML (2009) T cell antigen receptor signaling and immunological synapse stability require myosin IIA. Nat Immunol 10(5):531-539. doi: 10.1038/ni.1723
143. Babich A, Li S, O'Connor RS, Milone MC, Freedman BD, Burkhardt JK (2012) F-actin polymerization and retrograde flow drive sustained PLCgamma1 signaling during T cell activation. J Cell Biol 197(6):775-787. doi: 10.1083/jcb.201201018
144. Jacobelli J, Chmura SA, Buxton DB, Davis MM, Krummel MF (2004) A single class II myosin modulates T cell motility and stopping, but not synapse formation. Nat Immunol 5(5):531-538. doi: 10.1038/ni1065
145. Hammer JA 3rd, Burkhardt JK (2013) Controversy and consensus regarding myosin II function at the immunological synapse. Curr Opin Immunol. doi: 10.1016/j.coi.2013.03.010
146. Liu X, Kapoor TM, Chen JK, Huse M (2013) Diacylglycerol promotes centrosome polarization in T cells via reciprocal localization of dynein and myosin II. Proc Natl Acad Sci USA 110(29):11976-11981. doi: 10.1073/pnas.1306180110
147. 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(1):95-106. doi: 10.1111/imr.12116
148. Huse M (2012) Microtubule-organizing center polarity and the immunological synapse: protein kinase C and beyond. Front Immunol 3:235
149. Sedwick CE, Morgan MM, Jusino L, Cannon JL, Miller J, Burkhardt JK (1999) TCR, LFA-1, and CD28 play unique and complementary roles in signaling T cell cytoskeletal reorganization. J Immunol 162(3):1367-1375
150. Kuhne MR, Lin J, Yablonski D, Mollenauer MN, Ehrlich LI, Huppa J, Davis MM, Weiss A (2003) Linker for activation of T cells, zeta-associated protein-70, and Src homology 2 domain-containing leukocyte protein-76 are required for TCR-induced microtubule-organizing center polarization. J Immunol 171(2):860-866
151. Lowin-Kropf B, Shapiro VS, Weiss A (1998) Cytoskeletal polarization of T cells is regulated by an immunoreceptor tyrosine-based activation motif-dependent mechanism. J Cell Biol 140(4):861-871
152. Quann EJ, Liu X, Altan-Bonnet G, Huse M (2011) A cascade of protein kinase C isozymes promotes cytoskeletal polarization in T cells. Nat Immunol 12(7):647-654. doi: 10.1038/ni.2033
153. Quann EJ, Merino E, Furuta T, Huse M (2009) Localized diacylglycerol drives the polarization of the microtubule-organizing center in T cells. Nat Immunol 10(6):627-635
154. Bertrand F, Esquerre M, Petit AE, Rodrigues M, Duchez S, Delon J, Valitutti S (2010) 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 185(5):2887-2894. doi: 10.4049/jimmunol.1000739
155. Bertrand F, Muller S, Roh KH, Laurent C, Dupre L, Valitutti S (2013) An initial and rapid step of lytic granule secretion precedes microtubule organizing center polarization at the cytotoxic T lymphocyte/target cell synapse. Proc Natl Acad Sci USA 110(15):6073-6078. doi: 10.1073/pnas.1218640110
156. Etienne-Manneville S (2008) Polarity proteins in migration and invasion. Oncogene 27(55):6970-6980. doi: 10.1038/onc.2008.347
157. Etienne-Manneville S, Hall A (2003) Cell polarity: Par6, aPKC and cytoskeletal crosstalk. Curr Opin Cell Biol 15(1):67-72
158. Li R, Gundersen GG (2008) Beyond polymer polarity: how the cytoskeleton builds a polarized cell. Nat Rev Mol Cell Biol 9(11):860-873
159. Ludford-Menting MJ, Oliaro J, Sacirbegovic F, Cheah ET, Pedersen N, Thomas SJ, Pasam A, Iazzolino R, Dow LE, Waterhouse NJ, Murphy A, Ellis S, Smyth MJ, Kershaw MH, Darcy PK, Humbert PO, Russell SM (2005) A network of PDZ-containing proteins regulates T cell polarity and morphology during migration and immunological synapse formation. Immunity 22(6):737-748
160. Combs J, Kim SJ, Tan S, Ligon LA, Holzbaur EL, Kuhn J, Poenie M (2006) Recruitment of dynein to the Jurkat immunological synapse. Proc Natl Acad Sci USA 103(40):14883-14888
161. Martin-Cofreces NB, Robles-Valero J, Cabrero JR, Mittelbrunn M, Gordon-Alonso M, Sung CH, Alarcon B, Vazquez J, Sanchez-Madrid F (2008) MTOC translocation modulates IS formation and controls sustained T cell signaling. J Cell Biol 182(5):951-962
162. Yi J, Wu X, Chung AH, Chen JK, Kapoor TM, Hammer JA (2013) Centrosome repositioning in T cells is biphasic and driven by microtubule end-on capture-shrinkage. J Cell Biol 202(5):779-792. doi: 10.1083/jcb.201301004
163. Andres-Delgado L, Anton OM, Bartolini F, Ruiz-Saenz A, Correas I, Gundersen GG, Alonso MA (2012) INF2 promotes the formation of detyrosinated microtubules necessary for centrosome reorientation in T cells. J Cell Biol 198(6):1025-1037. doi: 10.1083/jcb.201202137
164. Eng CH, Huckaba TM, Gundersen GG (2006) The formin mDia regulates GSK3beta through novel PKCs to promote microtubule stabilization but not MTOC reorientation in migrating fibroblasts. Mol Biol Cell 17(12):5004-5016. doi: 10.1091/mbc.E05-10-0914
165. Wen Y, Eng CH, Schmoranzer J, Cabrera-Poch N, Morris EJ, Chen M, Wallar BJ, Alberts AS, Gundersen GG (2004) EB1 and APC bind to mDia to stabilize microtubules downstream of Rho and promote cell migration. Nat Cell Biol 6(9):820-830
166. Andres-Delgado L, Anton OM, Alonso MA (2013) Centrosome polarization in T cells: a task for formins. Front Immunol 4:191. doi: 10.3389/fimmu.2013.00191
167. Chesarone MA, DuPage AG, Goode BL (2010) Unleashing formins to remodel the actin and microtubule cytoskeletons. Nat Rev Mol Cell Biol 11(1):62-74. doi: 10.1038/nrm2816
168. Beal AM, Anikeeva N, Varma R, Cameron TO, Norris PJ, Dustin ML, Sykulev Y (2008) Protein kinase C theta regulates stability of the peripheral adhesion ring junction and contributes to the sensitivity of target cell lysis by CTL. J Immunol 181(7):4815-4824
169. Sasahara Y, Rachid R, Byrne MJ, de la Fuente MA, Abraham RT, Ramesh N, Geha RS (2002) Mechanism of recruitment of WASP to the immunological synapse and of its activation following TCR ligation. Mol Cell 10(6):1269-1281
170. Dong X, Patino-Lopez G, Candotti F, Shaw S (2007) Structure-function analysis of the WIP role in T cell receptor-stimulated NFAT activation: evidence that WIP-WASP dissociation is not required and that the WIP NH2 terminus is inhibitory. J Biol Chem 282(41):30303-30310. doi: 10.1074/jbc.M704972200
171. Campi G, Varma R, Dustin ML (2005) Actin and agonist MHC-peptide complex-dependent T cell receptor microclusters as scaffolds for signaling. J Exp Med 202(8):1031-1036
172. Yokosuka T, Sakata-Sogawa K, Kobayashi W, Hiroshima M, Hashimoto-Tane A, Tokunaga M, Dustin ML, Saito T (2005) Newly generated T cell receptor microclusters initiate and sustain T cell activation by recruitment of Zap70 and SLP-76. Nat Immunol 6(12):1253-1262
173. Hashimoto-Tane A, Yokosuka T, Sakata-Sogawa K, Sakuma M, Ishihara C, Tokunaga M, Saito T (2011) Dynein-driven transport of T cell receptor microclusters regulates immune synapse formation and T cell activation. Immunity 34(6):919-931. doi: 10.1016/j.immuni.2011.05.012
174. Vardhana S, Choudhuri K, Varma R, Dustin ML (2010) Essential role of ubiquitin and TSG101 protein in formation and function of the central supramolecular activation cluster. Immunity 32(4):531-540. doi: 10.1016/j.immuni.2010.04.005
175. Mossman KD, Campi G, Groves JT, Dustin ML (2005) Altered TCR signaling from geometrically repatterned immunological synapses. Science 310(5751):1191-1193
176. Anitei M, Hoflack B (2012) Bridging membrane and cytoskeleton dynamics in the secretory and endocytic pathways. Nat Cell Biol 14(1):11-19
177. Chaturvedi A, Martz R, Dorward D, Waisberg M, Pierce SK (2011) Endocytosed BCRs sequentially regulate MAPK and Akt signaling pathways from intracellular compartments. Nat Immunol 12(11):1119-1126. doi: 10.1038/ni.2116
178. 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(5425):221-227
179. Hyun YM, Lefort CT, Kim M (2009) Leukocyte integrins and their ligand interactions. Immunol Res. doi: 10.1007/s12026-009-8101-1
180. Kinashi T (2005) Intracellular signalling controlling integrin activation in lymphocytes. Nat Rev 5(7):546-559. doi: 10.1038/nri1646
181. Nolz JC, Nacusi LP, Segovis CM, Medeiros RB, Mitchell JS, Shimizu Y, Billadeau DD (2008) The WAVE2 complex regulates T cell receptor signaling to integrins via Abl- and CrkL-C3G-mediated activation of Rap1. J Cell Biol 182(6):1231-1244
182. Wernimont SA, Wiemer AJ, Bennin DA, Monkley SJ, Ludwig T, Critchley DR, Huttenlocher A (2011) Contact-dependent T cell activation and T cell stopping require talin1. J Immunol 187(12):6256-6267. doi: 10.4049/jimmunol.1102028
183. Nguyen K, Sylvain NR, Bunnell SC (2008) T cell costimulation via the integrin VLA-4 inhibits the actin-dependent centralization of signaling microclusters containing the adaptor SLP-76. Immunity 28(6):810-821. doi: 10.1016/j.immuni.2008.04.019
184. Beal AM, Anikeeva N, Varma R, Cameron TO, Vasiliver-Shamis G, Norris PJ, Dustin ML, Sykulev Y (2009) Kinetics of early T cell receptor signaling regulate the pathway of lytic granule delivery to the secretory domain. Immunity 31(4):632-642. doi: 10.1016/j.immuni.2009.09.004
185. Natkanski E, Lee WY, Mistry B, Casal A, Molloy JE, Tolar P (2013) B cells use mechanical energy to discriminate antigen affinities. Science 340(6140):1587-1590. doi: 10.1126/science.1237572
186. Zhang F, Wen Y, Guo X (2014) CRISPR/Cas9 for genome editing: progress, implications and challenges. Hum Mol Genet. doi: 10.1093/hmg/ddu125