Molecular Regulation of Cytoskeletal Rearrangements During T Cell Signalling

  • Theresia E. B. Stradal
  • Rico Pusch
  • Stefanie KlicheEmail author
Part of the Results and Problems in Cell Differentiation book series (RESULTS, volume 43)


Regulation of the cytoskeleton in cells of the haematopoietic system is essential for fulfilling diverse tasks such as migration towards a chemoattractant, phagocytosis or cell–cell communication. This is particularly true for the many types of T cells, which are at the foundation of the adaptive immune system in vertebrates. Deregulation of actin filament turnover is known to be involved in the development of severe immunodeficiencies or immunoproliferative diseases. Therefore, molecular dissection of signalling complexes and effector molecules, which leads to controlled cytoskeletal assembly, has been the focus of immunological research in the last decade.

In the past, cytoskeletal remodelling was frequently understood as the finish line of signalling, while today it becomes increasingly evident that actin and microtubule dynamics are required for proper signal transmission in many processes such as T cell activation. Significant effort is made in many laboratories to further elucidate the contribution of cytoskeletal remodelling to immune function.

The objective of this article is to summarise the current knowledge on how actin and microtubules are reorganised to support the formation of structures as diverse as the immunological synapse and peripheral protrusions during cell migration.

TCR CD28 Actin Tubulin Cytoskeleton Immunological synapse 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.



The work was funded in part by the DFG (KL1292/5-1 to SK and For471 to TEBS). We thank Dr. Martin Kliche for preparation of the schematic figures and Dr. Klemens Rottner for helpful discussions and critically reading the manuscript.


  1. 1.
    Acuto O, Michel F (2003) CD28-mediated co-stimulation: a quantitative support for TCR signalling. Nat Rev Immunol 3:939–951 PubMedGoogle Scholar
  2. 2.
    Anton IM, de la Fuente MA, Sims TN, Freeman S, Ramesh N, Hartwig JH, Dustin ML, Geha RS (2002) WIP deficiency reveals a differential role for WIP and the actin cytoskeleton in T and B cell activation. Immunity 16:193–204 PubMedGoogle Scholar
  3. 3.
    Aspenstrom P, Lindberg U, Hall A (1996) Two GTPases, Cdc42 and Rac, bind directly to a protein implicated in the immunodeficiency disorder Wiskott–Aldrich syndrome. Curr Biol 6:70–75 PubMedGoogle Scholar
  4. 4.
    August A, Gibson S, Kawakami Y, Kawakami T, Mills GB, Dupont B (1994) CD28 is associated with and induces the immediate tyrosine phosphorylation and activation of the Tec family kinase ITK/EMT in the human Jurkat leukemic T cell line. Proc Natl Acad Sci USA 91:9347–9351 PubMedGoogle Scholar
  5. 5.
    Badolato R, Sozzani S, Malacarne F, Bresciani S, Fiorini M, Borsatti A, Albertini A, Mantovani A, Ugazio AG, Notarangelo LD (1998) Monocytes from Wiskott–Aldrich patients display reduced chemotaxis and lack of cell polarization in response to monocyte chemoattractant protein-1 and formyl-methionyl-leucyl-phenylalanine. J Immunol 161:1026–1033 PubMedGoogle Scholar
  6. 6.
    Badour K, Zhang J, Siminovitch KA (2004) Involvement of the Wiskott–Aldrich syndrome protein and other actin regulatory adaptors in T cell activation. Semin Immunol 16:395–407 PubMedGoogle Scholar
  7. 7.
    Bear JE, Rawls JF, Saxe CL 3rd (1998) SCAR a WASP-related protein isolated as a suppressor of receptor defects in late Dictyostelium development. J Cell Biol 142:1325–1335 PubMedGoogle Scholar
  8. 8.
    Benesch S, Lommel S, Steffen A, Stradal TE, Scaplehorn N, Way M, Wehland J, Rottner K (2002) Phosphatidylinositol 4,5-bisphosphate (PIP2)-induced vesicle movement depends on N-WASP and involves Nck WIP and Grb2. J Biol Chem 277:37771–37776 PubMedGoogle Scholar
  9. 9.
    Benesch S, Polo S, Lai FP, Anderson KI, Stradal TE, Wehland J, Rottner K (2005) N-WASP deficiency impairs EGF internalization and actin assembly at clathrin-coated pits. J Cell Sci 118:3103–3115 PubMedGoogle Scholar
  10. 10.
    Beningo KA, Wang YL (2002) Flexible substrata for the detection of cellular traction forces. Trends Cell Biol 12:79–84 PubMedGoogle Scholar
  11. 11.
    Blagg SL, Stewart M, Sambles C, Insall RH (2003) PIR121 regulates pseudopod dynamics and SCAR activity in Dictyostelium. Curr Biol 13:1480–1487 PubMedGoogle Scholar
  12. 12.
    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 PubMedGoogle Scholar
  13. 13.
    Bluestone JA (1995) New perspectives of CD28-B7-mediated T cell costimulation. Immunity 2:555–559 PubMedGoogle Scholar
  14. 14.
    Bos JL, de Bruyn K, Enserink J, Kuiperij B, Rangarajan S, Rehmann H, Riedl J, de Rooij J, van Mansfeld F, Zwartkruis F (2003) The role of Rap1 in integrin-mediated cell adhesion. Biochem Soc Trans 31:83–86 PubMedGoogle Scholar
  15. 15.
    Bromley SK, Burack WR, Johnson KG, Somersalo K, Sims TN, Sumen C, Davis MM, Shaw AS, Allen PM, Dustin ML (2001a) The immunological synapse. Annu Rev Immunol 19:375–396 PubMedGoogle Scholar
  16. 16.
    Bromley SK, Iaboni A, Davis SJ, Whitty A, Green JM, Shaw AS, Weiss A, Dustin ML (2001b) The immunological synapse and CD28-CD80 interactions. Nat Immunol 2:1159–1166 PubMedGoogle Scholar
  17. 17.
    Brunner D (2002) How to grab a microtubule on the move. Dev Cell 3:2–4 PubMedGoogle Scholar
  18. 18.
    Burns S, Cory GO, Vainchenker W, Thrasher AJ (2004) Mechanisms of WASp-mediated hematologic and immunologic disease. Blood 104:3454–3462 PubMedGoogle Scholar
  19. 19.
    Cantrell DA (2003) GTPases and T cell activation. Immunol Rev 192:122–130 PubMedGoogle Scholar
  20. 20.
    Carlier MF, Nioche P, Broutin-L'Hermite I, Boujemaa R, Le Clainche C, Egile C, Garbay C, Ducruix A, Sansonetti P, Pantaloni D (2000) GRB2 links signaling to actin assembly by enhancing interaction of neural Wiskott–Aldrich syndrome protein (N-WASp) with actin-related protein (ARP2/3) complex. J Biol Chem 275:21946–21952 PubMedGoogle Scholar
  21. 21.
    Castellano F, Le Clainche C, Patin D, Carlier MF, Chavrier P (2001) A WASp-VASP complex regulates actin polymerization at the plasma membrane. Embo J 20:5603–5614 PubMedGoogle Scholar
  22. 22.
    Chen L (2004) Co-inhibitory molecules of the B7-CD28 family in the control of T cell immunity. Nat Rev Immunol 4:336–347 PubMedGoogle Scholar
  23. 23.
    Compton HL, Farrell JP (2002) CD28 costimulation and parasite dose combine to influence the susceptibility of BALB/c mice to infection with Leishmania major. J Immunol 168:1302–1308 PubMedGoogle Scholar
  24. 24.
    Coppolino MG, Krause M, Hagendorff P, Monner DA, Trimble W, Grinstein S, Wehland J, Sechi AS (2001) Evidence for a molecular complex consisting of Fyb/SLAP SLP-76 Nck VASP and WASP that links the actin cytoskeleton to Fcgamma receptor signalling during phagocytosis. J Cell Sci 114:4307–4318 PubMedGoogle Scholar
  25. 25.
    Cory GO, Cramer R, Blanchoin L, Ridley AJ (2003) Phosphorylation of the WASP-VCA domain increases its affinity for the Arp2/3 complex and enhances actin polymerization by WASP. Mol Cell 11:1229–1239 PubMedGoogle Scholar
  26. 26.
    Cory GO, Garg R, Cramer R, Ridley AJ (2002) Phosphorylation of tyrosine 291 enhances the ability of WASp to stimulate actin polymerization and filopodium formation. Wiskott–Aldrich Syndrome protein. J Biol Chem 277:45115–45121 PubMedGoogle Scholar
  27. 27.
    Daley GQ, Van Etten RA, Baltimore D (1990) Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science 247:824–830 PubMedGoogle Scholar
  28. 28.
    Davis DM, Dustin ML (2004) What is the importance of the immunological synapse? Trends Immunol 25:323–327 PubMedGoogle Scholar
  29. 29.
    DeMali KA, Wennerberg K, Burridge K (2003) Integrin signaling to the actin cytoskeleton. Curr Opin Cell Biol 15:572–582 PubMedGoogle Scholar
  30. 30.
    Depoil D, Zaru R, Guiraud M, Chauveau A, Harriague J, Bismuth G, Utzny C, Muller S, Valitutti S (2005) Immunological synapses are versatile structures enabling selective T cell polarization. Immunity 22:185–194 PubMedGoogle Scholar
  31. 31.
    Derry JM, Ochs HD, Francke U (1994) Isolation of a novel gene mutated in Wiskott–Aldrich syndrome. Cell 78:635–644 PubMedGoogle Scholar
  32. 32.
    Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, Lydon NB, Kantarjian H, Capdeville R, Ohno-Jones S, Sawyers CL (2001) Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 344:1031–1037 PubMedGoogle Scholar
  33. 33.
    Dutt P, Wang JF, Groopman JE (1998) Stromal cell-derived factor-1 alpha and stem cell factor/kit ligand share signaling pathways in hemopoietic progenitors: a potential mechanism for cooperative induction of chemotaxis. J Immunol 161:3652–3658 PubMedGoogle Scholar
  34. 34.
    Eden S, Rohatgi R, Podtelejnikov AV, Mann M, Kirschner MW (2002) Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck. Nature 418:790–793 PubMedGoogle Scholar
  35. 35.
    Engqvist-Goldstein AE, Drubin DG (2003) Actin assembly and endocytosis: from yeast to mammals. Annu Rev Cell Dev Biol 19:287–332 PubMedGoogle Scholar
  36. 36.
    Entschladen F, Gunzer M, Scheuffele CM, Niggemann B, Zanker KS (2000) T lymphocytes and neutrophil granulocytes differ in regulatory signaling and migratory dynamics with regard to spontaneous locomotion and chemotaxis. Cell Immunol 199:104–114 PubMedGoogle Scholar
  37. 37.
    Entschladen F, Maaser K, Gunzer M, Niggemann B, Zanker KS, Friedl P (1998) Distinct dynamics and regulatory signal transduction of cell migration: lessons from dendritic cells tumor cells and T lymphocytes. In: Mihich E, Croce C (eds) The biology of tumors. Plenum, New York, pp 43–49 Google Scholar
  38. 38.
    Entschladen F, Zanker KS (2000) Locomotion of tumor cells: a molecular comparison to migrating pre- and postmitotic leukocytes. J Cancer Res Clin Oncol 126:671–681 PubMedGoogle Scholar
  39. 39.
    Erck C, Frank R, Wehland J (2000) Tubulin-tyrosine ligase: a long-lasting enigma. Neurochem Res 25:5–10 PubMedGoogle Scholar
  40. 40.
    Erck C, Peris L, Andrieux A, Meissirel C, Gruber AD, Vernet M, Schweitzer A, Saoudi Y, Pointu H, Bosc C et al (2005) A vital role of tubulin-tyrosine-ligase for neuronal organization. Proc Natl Acad Sci USA 102:7853–7858 PubMedGoogle Scholar
  41. 41.
    Etienne-Manneville S (2004a) Actin and microtubules in cell motility: which one is in control? Traffic 5:470–477 PubMedGoogle Scholar
  42. 42.
    Etienne-Manneville S (2004b) Cdc42—the centre of polarity. J Cell Sci 117:1291–1300 PubMedGoogle Scholar
  43. 43.
    Etienne-Manneville S, Hall A (2003) Cdc42 regulates GSK-3beta and adenomatous polyposis coli to control cell polarity. Nature 421:753–756 PubMedGoogle Scholar
  44. 44.
    Friedl P, Gunzer M (2001) Interaction of T cells with APCs: the serial encounter model. Trends Immunol 22:187–191 PubMedGoogle Scholar
  45. 45.
    Friedl P, Storim J (2004) Diversity in immune-cell interactions: states and functions of the immunological synapse. Trends Cell Biol 14:557–567 PubMedGoogle Scholar
  46. 46.
    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 90:3089–3097 PubMedGoogle Scholar
  47. 47.
    Goldman JM, Melo JV (2003) Chronic myeloid leukemia—advances in biology and new approaches to treatment. N Engl J Med 349:1451–1464 PubMedGoogle Scholar
  48. 48.
    Gudmundsdottir H, Wells AD, Turka LA (1999) Dynamics and requirements of T cell clonal expansion in vivo at the single-cell level: effector function is linked to proliferative capacity. J Immunol 162:5212–5223 PubMedGoogle Scholar
  49. 49.
    Gundelfinger ED, Kessels MM, Qualmann B (2003) Temporal and spatial coordination of exocytosis and endocytosis. Nat Rev Mol Cell Biol 4:127–139 PubMedGoogle Scholar
  50. 50.
    Gundersen GG (2002) Evolutionary conservation of microtubule-capture mechanisms. Nat Rev Mol Cell Biol 3:296–304 PubMedGoogle Scholar
  51. 51.
    Gundersen GG, Cook TA (1999) Microtubules and signal transduction. Curr Opin Cell Biol 11:81–94 PubMedGoogle Scholar
  52. 52.
    Gundersen GG, Gomes ER, Wen Y (2004) Cortical control of microtubule stability and polarization. Curr Opin Cell Biol 16:106–112 PubMedGoogle Scholar
  53. 53.
    Gunzer M, Schafer A, Borgmann S, Grabbe S, Zanker KS, Brocker EB, Kampgen E, Friedl P (2000) Antigen presentation in extracellular matrix: interactions of T cells with dendritic cells are dynamic, short lived and sequential. Immunity 13:323–332 PubMedGoogle Scholar
  54. 54.
    Gunzer M, Weishaupt C, Hillmer A, Basoglu Y, Friedl P, Dittmar KE, Kolanus W, Varga G, Grabbe S (2004) A spectrum of biophysical interaction modes between T cells and different antigen-presenting cells during priming in 3-D collagen and in vivo. Blood 104:2801–2809 PubMedGoogle Scholar
  55. 55.
    Haddad E, Zugaza JL, Louache F, Debili N, Crouin C, Schwarz K, Fischer A, Vainchenker W, Bertoglio J (2001) The interaction between Cdc42 and WASP is required for SDF-1-induced T lymphocyte chemotaxis. Blood 97:33–38 PubMedGoogle Scholar
  56. 56.
    Haggarty SJ, Koeller KM, Wong JC, Butcher RA, Schreiber SL (2003) Multidimensional chemical genetic analysis of diversity-oriented synthesis-derived deacetylase inhibitors using cell-based assays. Chem Biol 10:383–396 PubMedGoogle Scholar
  57. 57.
    Hall A (1998) Rho GTPases and the actin cytoskeleton. Science 279:509–514 PubMedGoogle Scholar
  58. 58.
    Hantschel O, Superti-Furga G (2004) Regulation of the c-Abl and Bcr-Abl tyrosine kinases. Nat Rev Mol Cell Biol 5:33–44 PubMedGoogle Scholar
  59. 59.
    Hehner SP, Hofmann TG, Dienz O, Droge W, Schmitz ML (2000) Tyrosine-phosphorylated Vav1 as a point of integration for T cell receptor- and CD28-mediated activation of JNK p38 and interleukin-2 transcription. J Biol Chem 275:18160–18171 PubMedGoogle Scholar
  60. 60.
    Herreros L, Rodriguez-Fernandez JL, Brown MC, Alonso-Lebrero JL, Cabanas C, Sanchez-Madrid F, Longo N, Turner CE, Sanchez-Mateos P (2000) Paxillin localizes to the lymphocyte microtubule organizing center and associates with the microtubule cytoskeleton. J Biol Chem 275:26436–26440 PubMedGoogle Scholar
  61. 61.
    Hestermann A, Rehberg M, Graf R (2002) Centrosomal microtubule plus end tracking proteins and their role in Dictyostelium cell dynamics. J Muscle Res Cell Motil 23:621–630 PubMedGoogle Scholar
  62. 62.
    Higgs HN (2005) Formin proteins: a domain-based approach. Trends Biochem Sci 30:342–353 PubMedGoogle Scholar
  63. 63.
    Higgs HN, Pollard TD (2001) Regulation of actin filament network formation through ARP2/3 complex: activation by a diverse array of proteins. Annu Rev Biochem 70:649–676 PubMedGoogle Scholar
  64. 64.
    Ho HY, Rohatgi R, Ma L, Kirschner MW (2001) CR16 forms a complex with N-WASP in brain and is a novel member of a conserved proline-rich actin-binding protein family. Proc Natl Acad Sci USA 98:11306–11311 PubMedGoogle Scholar
  65. 65.
    Ho HY, Rohatgi R, Lebensohn AM, Le M, Li J, Gygi SP, Kirschner MW (2004) Toca-1 mediates Cdc42-dependent actin nucleation by activating the N-WASP-WIP complex. Cell 118:203–216 PubMedGoogle Scholar
  66. 66.
    Hogg N, Laschinger M, Giles K, McDowall A (2003) T cell integrins: more than just sticking points. J Cell Sci 116:4695–4705 PubMedGoogle Scholar
  67. 67.
    Horejsi V, Zhang W, Schraven B (2004) Transmembrane adaptor proteins: organizers of immunoreceptor signalling. Nat Rev Immunol 4:603–616 PubMedGoogle Scholar
  68. 68.
    Horwitz AR, Parsons JT (1999) Cell migration—movin' on. Science 286:1102–1103 PubMedGoogle Scholar
  69. 69.
    Hubbert C, Guardiola A, Shao R, Kawaguchi Y, Ito A, Nixon A, Yoshida M, Wang XF, Yao TP (2002) HDAC6 is a microtubule-associated deacetylase. Nature 417:455–458 PubMedGoogle Scholar
  70. 70.
    Huppa JB, Davis MM (2003) T cell-antigen recognition and the immunological synapse. Nat Rev Immunol 3:973–983 PubMedGoogle Scholar
  71. 71.
    Hussain NK, Jenna S, Glogauer M, Quinn CC, Wasiak S, Guipponi M, Antonarakis SE, Kay BK, Stossel TP, Lamarche-Vane N, McPherson PS (2001) Endocytic protein intersectin-l regulates actin assembly via Cdc42 and N-WASP. Nat Cell Biol 3:927–932 PubMedGoogle Scholar
  72. 72.
    Innocenti M, Zucconi A, Disanza A, Frittoli E, Areces LB, Steffen A, Stradal TE, Di Fiore PP, Carlier MF, Scita G (2004) Abi1 is essential for the formation and activation of a WAVE2 signalling complex. Nat Cell Biol 6:319–327 PubMedGoogle Scholar
  73. 73.
    Innocenti M, Gerboth S, Rottner K, Lai FPL, Hertzog M, Stradal TEB, Frittoli E, Didry D, Polo S, Disanza A et al (2005) Abi1 regulates the activity of N-WASP and WAVE in distinct actin-based processes. Nat Cell Biol 7:969–976 PubMedGoogle Scholar
  74. 74.
    Janetopoulos C, Ma L, Devreotes PN, Iglesias PA (2004) Chemoattractant-induced phosphatidylinositol 3,4,5-trisphosphate accumulation is spatially amplified and adapts independent of the actin cytoskeleton. Proc Natl Acad Sci USA 101:8951–8956 PubMedGoogle Scholar
  75. 75.
    Jones GE, Zicha D, Dunn GA, Blundell M, Thrasher A (2002) Restoration of podosomes and chemotaxis in Wiskott–Aldrich syndrome macrophages following induced expression of WASp. Int J Biochem Cell Biol 34:806–815 PubMedGoogle Scholar
  76. 76.
    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 68:1329–1332 PubMedGoogle Scholar
  77. 77.
    Kessels MM, Qualmann B (2004) The syndapin protein family: linking membrane trafficking with the cytoskeleton. J Cell Sci 117:3077–3086 PubMedGoogle Scholar
  78. 78.
    Kim CH, Broxmeyer HE (1999) Chemokines: signal lamps for trafficking of T and B cells for development and effector function. J Leukoc Biol 65:6–15 PubMedGoogle Scholar
  79. 79.
    Kim HH, Tharayil M, Rudd CE (1998) Growth factor receptor-bound protein 2 SH2/SH3 domain binding to CD28 and its role in co-signaling. J Biol Chem 273:296–301 PubMedGoogle Scholar
  80. 80.
    Kinbara K, Goldfinger LE, Hansen M, Chou FL, Ginsberg MH (2003) Ras GTPases: integrins' friends or foes? Nat Rev Mol Cell Biol 4:767–776 PubMedGoogle Scholar
  81. 81.
    King CL, Xianli J, June CH, Abe R, Lee KP (1996) CD28-deficient mice generate an impaired Th2 response to Schistosoma mansoni infection. Eur J Immunol 26:2448–2455 PubMedGoogle Scholar
  82. 82.
    Kliche S, Lindquist JA, Schraven B (2004) Transmembrane adapters: structure biochemistry and biology. Semin Immunol 16:367–377 PubMedGoogle Scholar
  83. 83.
    Kondo S, Kooshesh F, Wang B, Fujisawa H, Sauder DN (1996) Contribution of the CD28 molecule to allergic and irritant-induced skin reactions in CD28 –/– mice. J Immunol 157:4822–4829 PubMedGoogle Scholar
  84. 84.
    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 16:331–343 PubMedGoogle Scholar
  85. 85.
    Krinzman SJ, De Sanctis GT, Cernadas M, Mark D, Wang Y, Listman J, Kobzik L, Donovan C, Nassr K, Katona I et al (1996) Inhibition of T cell costimulation abrogates airway hyperresponsiveness in a murine model. J Clin Invest 98:2693–2699 PubMedCrossRefGoogle Scholar
  86. 86.
    Kuhn JR, Poenie M (2002) Dynamic polarization of the microtubule cytoskeleton during CTL-mediated killing. Immunity 16:111–121 PubMedGoogle Scholar
  87. 87.
    Kuhn JR, Wu Z, Poenie M (2001) Modulated polarization microscopy: a promising new approach to visualizing cytoskeletal dynamics in living cells. Biophys J 80:972–985 PubMedCrossRefGoogle Scholar
  88. 88.
    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 171:860–866 PubMedGoogle Scholar
  89. 89.
    Kunda P, Craig G, Dominguez V, Baum B (2003) Abi Sra1 and Kette control the stability and localization of SCAR/WAVE to regulate the formation of actin-based protrusions. Curr Biol 13:1867–1875 PubMedGoogle Scholar
  90. 90.
    Kupfer A, Kupfer H (2003) Imaging immune cell interactions and functions: SMACs and the immunological synapse. Semin Immunol 15:295–300 PubMedGoogle Scholar
  91. 91.
    Kupfer A, Dennert G, Singer SJ (1985) The reorientation of the Golgi apparatus and the microtubule-organizing center in the cytotoxic effector cell is a prerequisite in the lysis of bound target cells. J Mol Cell Immunol 2:37–49 PubMedGoogle Scholar
  92. 92.
    Kupfer A, Mosmann TR, Kupfer H (1991) Polarized expression of cytokines in cell conjugates of helper T cells and splenic B cells. Proc Natl Acad Sci USA 88:775–779 PubMedGoogle Scholar
  93. 93.
    Kupfer H, Monks CR, Kupfer A (1994) Small splenic B cells that bind to antigen-specific T helper (Th) cells and face the site of cytokine production in the Th cells selectively proliferate: immunofluorescence microscopic studies of Th–B antigen-presenting cell interactions. J Exp Med 179:1507–1515 PubMedGoogle Scholar
  94. 94.
    Laudanna C, Kim JY, Constantin G, Butcher E (2002) Rapid leukocyte integrin activation by chemokines. Immunol Rev 186:37–46 PubMedGoogle Scholar
  95. 95.
    LeDizet M, Piperno G (1987) Identification of an acetylation site of Chlamydomonas alpha-tubulin. Proc Natl Acad Sci USA 84:5720–5724 PubMedGoogle Scholar
  96. 96.
    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 PubMedGoogle Scholar
  97. 97.
    Lee KH, Dinner AR, Tu C, Campi G, Raychaudhuri S, Varma R, Sims TN, Burack WR, Wu H, Wang J et al (2003) The immunological synapse balances T cell receptor signaling and degradation. Science 302:1218–1222 PubMedGoogle Scholar
  98. 98.
    Lenschow DJ, Walunas TL, Bluestone JA (1996) CD28/B7 system of T cell costimulation. Annu Rev Immunol 14:233–258 PubMedGoogle Scholar
  99. 99.
    L'Hernault SW, Rosenbaum JL (1985) Chlamydomonas alpha-tubulin is posttranslationally modified by acetylation on the epsilon-amino group of a lysine. Biochemistry 24:473–478 PubMedGoogle Scholar
  100. 100.
    Lorenzi R, Brickell PM, Katz DR, Kinnon C, Thrasher AJ (2000) Wiskott–Aldrich syndrome protein is necessary for efficient IgG-mediated phagocytosis. Blood 95:2943–2946 PubMedGoogle Scholar
  101. 101.
    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 140:861–871 PubMedGoogle Scholar
  102. 102.
    Lucas JA, Miller AT, Atherly LO, Berg LJ (2003) The role of Tec family kinases in T cell development and function. Immunol Rev 191:119–138 PubMedGoogle Scholar
  103. 103.
    Lucas PJ, Negishi I, Nakayama K, Fields LE, Loh DY (1995) Naive CD28-deficient T cells can initiate but not sustain an in vitro antigen-specific immune response. J Immunol 154:5757–5768 PubMedGoogle Scholar
  104. 104.
    Machesky LM, Insall RH (1998) Scar1 and the related Wiskott–Aldrich syndrome protein WASP regulate the actin cytoskeleton through the Arp2/3 complex. Curr Biol 8:1347–1356 PubMedGoogle Scholar
  105. 105.
    Machesky LM, Mullins RD, Higgs HN, Kaiser DA, Blanchoin L, May RC, Hall ME, Pollard TD (1999) Scar a WASp-related protein activates nucleation of actin filaments by the Arp2/3 complex. Proc Natl Acad Sci USA 96:3739–3744 PubMedGoogle Scholar
  106. 106.
    MacRae TH (1997) Tubulin post-translational modifications—enzymes and their mechanisms of action. Eur J Biochem 244:265–278 PubMedGoogle Scholar
  107. 107.
    Majstoravich S, Zhang J, Nicholson-Dykstra S, Linder S, Friedrich W, Siminovitch KA, Higgs HN (2004) Lymphocyte microvilli are dynamic actin-dependent structures that do not require Wiskott–Aldrich syndrome protein (WASp) for their morphology. Blood 104:1396–1403 PubMedGoogle Scholar
  108. 108.
    Martinez-Quiles N, Rohatgi R, Anton IM, Medina M, Saville SP, Miki H, Yamaguchi H, Takenawa T, Hartwig JH, Geha RS, Ramesh N (2001) WIP regulates N-WASP-mediated actin polymerization and filopodium formation. Nat Cell Biol 3:484–491 PubMedGoogle Scholar
  109. 109.
    McGavin MK, Badour K, Hardy LA, Kubiseski TJ, Zhang J, Siminovitch KA (2001) The intersectin 2 adaptor links Wiskott–Aldrich syndrome protein (WASp)-mediated actin polymerization to T cell antigen receptor endocytosis. J Exp Med 194:1777–1787 PubMedGoogle Scholar
  110. 110.
    Merrifield CJ, Feldman ME, Wan L, Almers W (2002) Imaging actin and dynamin recruitment during invagination of single clathrin-coated pits. Nat Cell Biol 4:691–698 PubMedGoogle Scholar
  111. 111.
    Merrifield CJ, Qualmann B, Kessels MM, Almers W (2004) Neural Wiskott–Aldrich syndrome protein (N-WASP) and the Arp2/3 complex are recruited to sites of clathrin-mediated endocytosis in cultured fibroblasts. Eur J Cell Biol 83:13–18 PubMedGoogle Scholar
  112. 112.
    Michel F, Attal-Bonnefoy G, Mangino G, Mise-Omata S, Acuto O (2001) CD28 as a molecular amplifier extending TCR ligation and signaling capabilities. Immunity 15:935–945 PubMedGoogle Scholar
  113. 113.
    Miki H, Suetsugu S, Takenawa T (1998) WAVE: a novel WASP-family protein involved in actin reorganization induced by Rac. Embo J 17:6932–6941 PubMedGoogle Scholar
  114. 114.
    Miletic AV, Swat M, Fujikawa K, Swat W (2003) Cytoskeletal remodeling in lymphocyte activation. Curr Opin Immunol 15:261–268 PubMedGoogle Scholar
  115. 115.
    Millard TH, Sharp SJ, Machesky LM (2004) Signalling to actin assembly via the WASP (Wiskott–Aldrich syndrome protein)-family proteins and the Arp2/3 complex. Biochem J 380:1–17 PubMedGoogle Scholar
  116. 116.
    Miller MJ, Wei SH, Cahalan MD, Parker I (2003) Autonomous T cell trafficking examined in vivo with intravital two-photon microscopy. Proc Natl Acad Sci USA 100:2604–2609 PubMedGoogle Scholar
  117. 117.
    Mittrucker HW, Kursar M, Kohler A, Hurwitz R, Kaufmann SH (2001) Role of CD28 for the generation and expansion of antigen-specific CD8(+) T lymphocytes during infection with Listeria monocytogenes. J Immunol 167:5620–5627 PubMedGoogle Scholar
  118. 118.
    Mizutani K, Miki H, He H, Maruta H, Takenawa T (2002) Essential role of neural Wiskott–Aldrich syndrome protein in podosome formation and degradation of extracellular matrix in src-transformed fibroblasts. Cancer Res 62:669–674 PubMedGoogle Scholar
  119. 119.
    Moreau V, Frischknecht F, Reckmann I, Vincentelli R, Rabut G, Stewart D, Way M (2000) A complex of N-WASP and WIP integrates signalling cascades that lead to actin polymerization. Nat Cell Biol 2:441–448 PubMedGoogle Scholar
  120. 120.
    Myers SA, Han JW, Lee Y, Firtel RA, Chung CY (2005) A Dictyostelium homologue of WASP is required for polarized F-actin assembly during chemotaxis. Mol Biol Cell 16:2191–2206 PubMedGoogle Scholar
  121. 121.
    Nagasawa T, Hirota S, Tachibana K, Takakura N, Nishikawa S, Kitamura Y, Yoshida N, Kikutani H, Kishimoto T (1996) Defects of B cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature 382:635–638 PubMedGoogle Scholar
  122. 122.
    Nikolai G, Niggemann B, Werner M, Zanker KS, Friedl P (1998) Direct and rapid induction of migration in human CD4+ T lymphocytes within three-dimensional collagen matrices mediated by signalling via CD3 and/or CD2. Immunology 95:62–68 PubMedGoogle Scholar
  123. 123.
    Nobes CD, Hall A (1995) Rho rac and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers lamellipodia and filopodia. Cell 81:53–62 PubMedGoogle Scholar
  124. 124.
    Okabe S, Fukuda S, Broxmeyer HE (2002) Activation of Wiskott–Aldrich syndrome protein and its association with other proteins by stromal cell-derived factor-1alpha is associated with cell migration in a T lymphocyte line. Exp Hematol 30:761–766 PubMedGoogle Scholar
  125. 125.
    Orange JS, Stone KD, Turvey SE, Krzewski K (2004) The Wiskott–Aldrich syndrome. Cell Mol Life Sci 61:2361–2385 PubMedGoogle Scholar
  126. 126.
    Pages F, Ragueneau M, Rottapel R, Truneh A, Nunes J, Imbert J, Olive D (1994) Binding of phosphatidylinositol-3-OH kinase to CD28 is required for T cell signalling. Nature 369:327–329 PubMedGoogle Scholar
  127. 127.
    Palazzo AF, Joseph HL, Chen YJ, Dujardin DL, Alberts AS, Pfister KK, Vallee RB, Gundersen GG (2001) Cdc42 dynein and dynactin regulate MTOC reorientation independent of Rho-regulated microtubule stabilization. Curr Biol 11:1536–1541 PubMedGoogle Scholar
  128. 128.
    Parent CA (2004) Making all the right moves: chemotaxis in neutrophils and Dictyostelium. Curr Opin Cell Biol 16:4–13 PubMedGoogle Scholar
  129. 129.
    Peacock JW, Jirik FR (1999) TCR activation inhibits chemotaxis toward stromal cell-derived factor-1: evidence for reciprocal regulation between CXCR4 and the TCR. J Immunol 162:215–223 PubMedGoogle Scholar
  130. 130.
    Pendergast AM, Witte ON (1987) Role of the ABL oncogene tyrosine kinase activity in human leukaemia. Baillieres Clin Haematol 1:1001–1020 PubMedGoogle Scholar
  131. 131.
    Poenie M, Kuhn J, Combs J (2004) Real-time visualization of the cytoskeleton and effector functions in T cells. Curr Opin Immunol 16:428–438 PubMedGoogle Scholar
  132. 132.
    Polevoda B, Sherman F (2002) The diversity of acetylated proteins. Genome Biol 3:reviews 0006 Google Scholar
  133. 133.
    Pollard TD, Borisy GG (2003) Cellular motility driven by assembly and disassembly of actin filaments. Cell 112:453–465 PubMedGoogle Scholar
  134. 134.
    Poo WJ, Conrad L, Janeway CA Jr (1988) Receptor-directed focusing of lymphokine release by helper T cells. Nature 332:378–380 PubMedGoogle Scholar
  135. 135.
    Qualmann B, Kessels MM (2002) Endocytosis and the cytoskeleton. Int Rev Cytol 220:93–144 PubMedGoogle Scholar
  136. 136.
    Radoja S, Saio M, Schaer D, Koneru M, Vukmanovic S, Frey AB (2001) CD8(+) tumor-infiltrating T cells are deficient in perforin-mediated cytolytic activity due to defective microtubule-organizing center mobilization and lytic granule exocytosis. J Immunol 167:5042–5051 PubMedGoogle Scholar
  137. 137.
    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 PubMedGoogle Scholar
  138. 138.
    Reichert P, Reinhardt RL, Ingulli E, Jenkins MK (2001) Cutting edge: in vivo identification of TCR redistribution and polarized IL-2 production by naive CD4 T cells. J Immunol 166:4278–4281 PubMedGoogle Scholar
  139. 139.
    Rodriguez-Fernandez JL, Gomez M, Luque A, Hogg N, Sanchez-Madrid F, Cabanas C (1999) The interaction of activated integrin lymphocyte function-associated antigen 1 with ligand intercellular adhesion molecule 1 induces activation and redistribution of focal adhesion kinase and proline-rich tyrosine kinase 2 in T lymphocytes. Mol Biol Cell 10:1891–1907 PubMedGoogle Scholar
  140. 140.
    Rogers SL, Wiedemann U, Stuurman N, Vale RD (2003) Molecular requirements for actin-based lamella formation in Drosophila S2 cells. J Cell Biol 162:1079–1088 PubMedGoogle Scholar
  141. 141.
    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 97:221–231 PubMedGoogle Scholar
  142. 142.
    Rohatgi R, Ho HY, Kirschner MW (2000) Mechanism of N-WASP activation by CDC42 and phosphatidylinositol 4,5-bisphosphate. J Cell Biol 150:1299–1310 PubMedGoogle Scholar
  143. 143.
    Rohatgi R, Nollau P, Ho HY, Kirschner MW, Mayer BJ (2001) Nck and phosphatidylinositol 4,5-bisphosphate synergistically activate actin polymerization through the N-WASP-Arp2/3 pathway. J Biol Chem 276:26448–26452 PubMedGoogle Scholar
  144. 144.
    Romero S, Le Clainche C, Didry D, Egile C, Pantaloni D, Carlier MF (2004) Formin is a processive motor that requires profilin to accelerate actin assembly and associated ATP hydrolysis. Cell 119:419–429 PubMedGoogle Scholar
  145. 145.
    Rudd CE, Schneider H (2003) Unifying concepts in CD28 ICOS and CTLA4 co-receptor signalling. Nat Rev Immunol 3:544–556 PubMedGoogle Scholar
  146. 146.
    Rulifson IC, Sperling AI, Fields PE, Fitch FW, Bluestone JA (1997) CD28 costimulation promotes the production of Th2 cytokines. J Immunol 158:658–665 PubMedGoogle Scholar
  147. 147.
    Salomon B, Bluestone JA (2001) Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation. Annu Rev Immunol 19:225–252 PubMedGoogle Scholar
  148. 148.
    Sancho D, Nieto M, Llano M, Rodriguez-Fernandez JL, Tejedor R, Avraham S, Cabanas C, Lopez-Botet M, Sanchez-Madrid F (2000) The tyrosine kinase PYK-2/RAFTK regulates natural killer (NK) cell cytotoxic response and is translocated and activated upon specific target cell recognition and killing. J Cell Biol 149:1249–1262 PubMedGoogle Scholar
  149. 149.
    Sancho D, Vicente-Manzanares M, Mittelbrunn M, Montoya MC, Gordon-Alonso M, Serrador JM, Sanchez-Madrid F (2002) Regulation of microtubule-organizing center orientation and actomyosin cytoskeleton rearrangement during immune interactions. Immunol Rev 189:84–97 PubMedGoogle Scholar
  150. 150.
    Schafer DA (2002) Coupling actin dynamics and membrane dynamics during endocytosis. Curr Opin Cell Biol 14:76–81 PubMedGoogle Scholar
  151. 151.
    Sechi AS, Buer J, Wehland J, Probst-Kepper M (2002) Changes in actin dynamics at the T cell/APC interface: implications for T cell anergy? Immunol Rev 189:98–110 PubMedGoogle Scholar
  152. 152.
    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 162:1367–1375 PubMedGoogle Scholar
  153. 153.
    Serrador JM, Cabrero JR, Sancho D, Mittelbrunn M, Urzainqui A, Sanchez-Madrid F (2004) HDAC6 deacetylase activity links the tubulin cytoskeleton with immune synapse organization. Immunity 20:417–428 PubMedGoogle Scholar
  154. 154.
    Shahinian A, Pfeffer K, Lee KP, Kundig TM, Kishihara K, Wakeham A, Kawai K, Ohashi PS, Thompson CB, Mak TW (1993) Differential T cell costimulatory requirements in CD28-deficient mice. Science 261:609–612 PubMedGoogle Scholar
  155. 155.
    Silvin C, Belisle B, Abo A (2001) A role for Wiskott–Aldrich syndrome protein in T cell receptor-mediated transcriptional activation independent of actin polymerization. J Biol Chem 276:21450–21457 PubMedGoogle Scholar
  156. 156.
    Small JV, Stradal T, Vignal E, Rottner K (2002) The lamellipodium: where motility begins. Trends Cell Biol 12:112–120 PubMedGoogle Scholar
  157. 157.
    Smith L, Wang Z, Smith JB (2003) Caspase processing activates atypical protein kinase C zeta by relieving autoinhibition and destabilizes the protein. Biochem J 375:663–671 PubMedGoogle Scholar
  158. 158.
    Snapper SB, Rosen FS, Mizoguchi E, Cohen P, Khan W, Liu CH, Hagemann TL, Kwan SP, Ferrini R, Davidson L et al (1998) Wiskott–Aldrich syndrome protein-deficient mice reveal a role for WASP in T but not B cell activation. Immunity 9:81–91 PubMedGoogle Scholar
  159. 159.
    Sossey-Alaoui K, Head K, Nowak N, Cowell JK (2003) Genomic organization and expression profile of the human and mouse WAVE gene family. Mamm Genome 14:314–322 PubMedGoogle Scholar
  160. 160.
    Steffen A, Rottner K, Ehinger J, Innocenti M, Scita G, Wehland J, Stradal TEB (2004) Sra-1 and Nap1 link Rac to actin assembly driving lamellipodia formation. Embo J 23:749–759 PubMedGoogle Scholar
  161. 161.
    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 PubMedGoogle Scholar
  162. 162.
    Stradal TEB, Rottner K, Disanza A, Confalioneri S, Innocenti M, Scita G (2004) Regulation of actin dynamics by WASP and WAVE family proteins. Trends Cell Biol 14:303–311 PubMedGoogle Scholar
  163. 163.
    Symons M, Derry JM, Karlak B, Jiang S, Lemahieu V, McCormick F, Francke U, Abo A (1996) Wiskott–Aldrich syndrome protein, a novel effector for the GTPase CDC42Hs, is implicated in actin polymerization. Cell 84:723–734 PubMedGoogle Scholar
  164. 164.
    Taunton J (2001) Actin filament nucleation by endosomes, lysosomes and secretory vesicles. Curr Opin Cell Biol 13:85–91 PubMedGoogle Scholar
  165. 165.
    Thrasher AJ (2002) WASp in immune-system organization and function. Nat Rev Immunol 2:635–646 PubMedGoogle Scholar
  166. 166.
    Tian L, Nelson DL, Stewart DM (2000) Cdc42-interacting protein 4 mediates binding of the Wiskott–Aldrich syndrome protein to microtubules. J Biol Chem 275:7854–7861 PubMedGoogle Scholar
  167. 167.
    Togni M, Lindquist J, Gerber A, Kolsch U, Hamm-Baarke A, Kliche S, Schraven B (2004) The role of adaptor proteins in lymphocyte activation. Mol Immunol 41:615–630 PubMedGoogle Scholar
  168. 168.
    Tskvitaria-Fuller I, Rozelle AL, Yin HL, Wulfing C (2003) Regulation of sustained actin dynamics by the TCR and costimulation as a mechanism of receptor localization. J Immunol 171:2287–2295 PubMedGoogle Scholar
  169. 169.
    Tsuchida M, Manthei ER, Knechtle SJ, Hamawy MM (1999) CD28 ligation induces rapid tyrosine phosphorylation of the linker molecule LAT in the absence of Syk and ZAP-70 tyrosine phosphorylation. Eur J Immunol 29:2354–2359 PubMedGoogle Scholar
  170. 170.
    Tybulewicz VL, Ardouin L, Prisco A, Reynolds LF (2003) Vav1: a key signal transducer downstream of the TCR. Immunol Rev 192:42–52 PubMedGoogle Scholar
  171. 171.
    Ueda M, Graf R, MacWilliams HK, Schliwa M, Euteneuer U (1997) Centrosome positioning and directionality of cell movements. Proc Natl Acad Sci USA 94:9674–9678 PubMedGoogle Scholar
  172. 172.
    Valitutti S, Dessing M, Aktories K, Gallati H, Lanzavecchia A (1995) Sustained signaling leading to T cell activation results from prolonged T cell receptor occupancy. Role of T cell actin cytoskeleton. J Exp Med 181:577–584 PubMedGoogle Scholar
  173. 173.
    Vallejo AN (2005) CD28 extinction in human T cells: altered functions and the program of T cell senescence. Immunol Rev 205:158–169 PubMedGoogle Scholar
  174. 174.
    Van Haastert PJ, Devreotes PN (2004) Chemotaxis: signalling the way forward. Nat Rev Mol Cell Biol 5:626–634 PubMedGoogle Scholar
  175. 175.
    Via CS, Rus V, Nguyen P, Linsley P, Gause WC (1996) Differential effect of CTLA4Ig on murine graft-versus-host disease (GVHD) development: CTLA4Ig prevents both acute and chronic GVHD development but reverses only chronic GVHD. J Immunol 157:4258–4267 PubMedGoogle Scholar
  176. 176.
    Volkov Y, Long A, Kelleher D (1998) Inside the crawling T cell: leukocyte function-associated antigen-1 cross-linking is associated with microtubule-directed translocation of protein kinase C isoenzymes beta(I) and delta. J Immunol 161:6487–6495 PubMedGoogle Scholar
  177. 177.
    Volkov Y, Long A, McGrath S, Ni Eidhin D, Kelleher D (2001) Crucial importance of PKC-beta(I) in LFA-1-mediated locomotion of activated T cells. Nat Immunol 2:508–514 PubMedGoogle Scholar
  178. 178.
    Vyas YM, Maniar H, Dupont B (2002) Visualization of signaling pathways and cortical cytoskeleton in cytolytic and noncytolytic natural killer cell immune synapses. Immunol Rev 189:161–178 PubMedGoogle Scholar
  179. 179.
    Wang JF, Park IW, Groopman JE (2000) Stromal cell-derived factor-1alpha stimulates tyrosine phosphorylation of multiple focal adhesion proteins and induces migration of hematopoietic progenitor cells: roles of phosphoinositide-3 kinase and protein kinase C. Blood 95:2505–2513 PubMedGoogle Scholar
  180. 180.
    Westermann S, Weber K (2003) Post-translational modifications regulate microtubule function. Nat Rev Mol Cell Biol 4:938–947 PubMedGoogle Scholar
  181. 181.
    Yamazaki D, Suetsugu S, Miki H, Kataoka Y, Nishikawa S, Fujiwara T, Yoshida N, Takenawa T (2003) WAVE2 is required for directed cell migration and cardiovascular development. Nature 424:452–456 PubMedGoogle Scholar
  182. 182.
    Yan C, Martinez-Quiles N, Eden S, Shibata T, Takeshima F, Shinkura R, Fujiwara Y, Bronson R, Snapper SB, Kirschner MW et al (2003) WAVE2 deficiency reveals distinct roles in embryogenesis and Rac-mediated actin-based motility. Embo J 22:3602–3612 PubMedGoogle Scholar
  183. 183.
    Yang WC, Ghiotto M, Barbarat B, Olive D (1999) The role of Tec protein-tyrosine kinase in T cell signaling. J Biol Chem 274:607–617 PubMedGoogle Scholar
  184. 184.
    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 171:1360–1368 PubMedGoogle Scholar
  185. 185.
    Zhang J, Shehabeldin A, da Cruz LA, Butler J, Somani AK, McGavin M, Kozieradzki I, dos Santos AO, Nagy A, Grinstein S et al (1999) Antigen receptor-induced activation and cytoskeletal rearrangement are impaired in Wiskott–Aldrich syndrome protein-deficient lymphocytes. J Exp Med 190:1329–1342 PubMedGoogle Scholar
  186. 186.
    Zhang Y, Li N, Caron C, Matthias G, Hess D, Khochbin S, Matthias P (2003) HDAC-6 interacts with and deacetylates tubulin and microtubules in vivo. Embo J 22:1168–1179 PubMedGoogle Scholar
  187. 187.
    Zicha D, Allen WE, Brickell PM, Kinnon C, Dunn GA, Jones GE, Thrasher AJ (1998) Chemotaxis of macrophages is abolished in the Wiskott–Aldrich syndrome. Br J Haematol 101:659–665 PubMedGoogle Scholar
  188. 188.
    Zigmond SH (2004) Formin-induced nucleation of actin filaments. Curr Opin Cell Biol 16:99–105 PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  • Theresia E. B. Stradal
    • 1
  • Rico Pusch
    • 2
  • Stefanie Kliche
    • 2
    Email author
  1. 1.Signalling and Motility GroupGerman Research Centre for Biotechnology (GBF)BraunschweigGermany
  2. 2.Institute of ImmunologyOtto von Guericke UniversityMagdeburgGermany

Personalised recommendations