Cellular and Molecular Life Sciences

, Volume 66, Issue 14, pp 2319–2328 | Cite as

Cytoskeleton–membrane interactions in membrane raft structure

  • Gurunadh R. Chichili
  • William RodgersEmail author


Cell membranes are structurally heterogeneous, composed of discrete domains with unique physical and biological properties. Membrane domains can form through a number of mechanisms involving lipid–lipid and protein–lipid interactions. One type of membrane domain is the cholesterol-dependent membrane raft. How rafts form remains a current topic in membrane biology. We review here evidence of structuring of rafts by the cortical actin cytoskeleton. This includes evidence that the actin cytoskeleton associates with rafts, and that many of the structural and functional properties of rafts require an intact actin cytoskeleton. We discuss the mechanisms of the actin-dependent raft organization, and the properties of the actin cytoskeleton in regulating raft-associated signaling events. We end with a discussion of membrane rafts and the actin cytoskeleton in T cell activation, which function synergistically to initiate the adaptive immune response.


Membrane rafts Actin cytoskeleton Phosphatidylinositol 4 5 bisphosphate T cell signaling Src family kinases 



This work was supported by NIH grant R01 GM070001 and Oklahoma Center for the advancement of Science and Technology grants HR08-084 (WR).


  1. 1.
    Rodgers W, Farris D, Mishra S (2005) Merging complexes: properties of membrane raft assembly during lymphocyte signaling. Trends Immunol 26:97–103PubMedCrossRefGoogle Scholar
  2. 2.
    Brown DA, London E (2000) Structure and function of sphingolipid- and cholesterol-rich membrane rafts. J Biol Chem 275:17221–17224PubMedCrossRefGoogle Scholar
  3. 3.
    Sharma P, Varma R, Sarasij RC, Ira, Gousset K, Krishnamoorthy G, Rao M, Mayor S (2004) Nanoscale organization of multiple GPI-anchored proteins in living cell membranes. Cell 116: 577–589Google Scholar
  4. 4.
    Zacharias DA, Violin JD, Newton AC, Tsien RY (2002) Partitioning of lipid-modified monomeric GFPs into membrane microdomains of live cells. Science 296:913–916PubMedCrossRefGoogle Scholar
  5. 5.
    Eggeling C, Ringemann C, Medda R, Schwarzmann G, Sandhoff K, Polyakova S, Belov VN, Hein B, von Middendorff C, Schonle A, Hell SW (2009) Direct observation of the nanoscale dynamics of membrane lipids in a living cell. Nature 457:1159–1162PubMedCrossRefGoogle Scholar
  6. 6.
    Jacobson K, Mouritsen OG, Anderson RG (2007) Lipid rafts: at a crossroad between cell biology and physics. Nat Cell Biol 9:7–14PubMedCrossRefGoogle Scholar
  7. 7.
    Yang B, Oo TN, Rizzo V (2006) Lipid rafts mediate H2O2 prosurvival effects in cultured endothelial cells. FASEB J 20:1501–1503PubMedCrossRefGoogle Scholar
  8. 8.
    Yamazaki S, Iwama A, Takayanagi S, Morita Y, Eto K, Ema H, Nakauchi H (2006) Cytokine signals modulated via lipid rafts mimic niche signals and induce hibernation in hematopoietic stem cells. EMBO J 25:3515–3523PubMedCrossRefGoogle Scholar
  9. 9.
    Furne C, Corset V, Herincs Z, Cahuzac N, Hueber AO, Mehlen P (2006) The dependence receptor DCC requires lipid raft localization for cell death signaling. Proc Natl Acad Sci USA 103:4128–4133PubMedCrossRefGoogle Scholar
  10. 10.
    Koenig A, Russell JQ, Rodgers WA, Budd RC (2008) Spatial differences in active caspase-8 defines its role in T cell activation versus cell death. Cell Death Differ 15:1701–1711PubMedCrossRefGoogle Scholar
  11. 11.
    Baruthio F, Quadroni M, Ruegg C, Mariotti A (2008) Proteomic analysis of membrane rafts of melanoma cells identifies protein patterns characteristic of the tumor progression stage. Proteomics 8:4733–4747PubMedCrossRefGoogle Scholar
  12. 12.
    Jury EC, Kabouridis PS, Flores-Borja F, Mageed RA, Isenberg DA (2004) Altered lipid raft-associated signaling and ganglioside expression in T lymphocytes from patients with systemic lupus erythematosus. J Clin Invest 113:1176–1187PubMedGoogle Scholar
  13. 13.
    Banfi C, Brioschi M, Wait R, Begum S, Gianazza E, Fratto P, Polvani G, Vitali E, Parolari A, Mussoni L, Tremoli E (2006) Proteomic analysis of membrane microdomains derived from both failing and non-failing human hearts. Proteomics 6:1976–1988PubMedCrossRefGoogle Scholar
  14. 14.
    Manes S, del Real G, Martinez AC (2003) Pathogens: raft hijackers. Nat Rev Immunol 3:557–568PubMedCrossRefGoogle Scholar
  15. 15.
    Marsh M, Helenius A (2006) Virus entry: open sesame. Cell 124:729–740PubMedCrossRefGoogle Scholar
  16. 16.
    Cambi A, de Lange F, van Maarseveen NM, Nijhuis M, Joosten B, van Dijk EM, de Bakker BI, Fransen JA, Bovee-Geurts PH, van Leeuwen FN, Van Hulst NF, Figdor CG (2004) Microdomains of the C-type lectin DC-SIGN are portals for virus entry into dendritic cells. J Cell Biol 164:145–155PubMedCrossRefGoogle Scholar
  17. 17.
    Bhattacharya B, Roy P (2008) Bluetongue virus outer capsid protein VP5 interacts with membrane lipid rafts via a snare domain. J Virol 82:10600–10612PubMedCrossRefGoogle Scholar
  18. 18.
    Simons K, Ikonen E (1997) Functional rafts in cell membranes. Nature 387:569–572PubMedCrossRefGoogle Scholar
  19. 19.
    Sengupta P, Baird B, Holowka D (2007) Lipid rafts, fluid/fluid phase separation, and their relevance to plasma membrane structure and function. Semin Cell Dev Biol 18:583–590PubMedCrossRefGoogle Scholar
  20. 20.
    Brown DA, Rose JK (1992) Sorting of GPI-anchored proteins to glycolipid-enriched membrane subdomains during transport to the apical cell surface. Cell 68:533–544PubMedCrossRefGoogle Scholar
  21. 21.
    Simons K, Toomre D (2000) Lipid rafts and signal transduction. Nat Mol Cell Biol Rev 1:31–39CrossRefGoogle Scholar
  22. 22.
    Chiantia S, Kahya N, Schwille P (2007) Raft domain reorganization driven by short- and long-chain ceramide: a combined AFM and FCS study. Langmuir 23:7659–7665PubMedCrossRefGoogle Scholar
  23. 23.
    Risselada HJ, Marrink SJ (2008) The molecular face of lipid rafts in model membranes. Proc Natl Acad Sci USA 105:17367–17372PubMedCrossRefGoogle Scholar
  24. 24.
    Sankaram MB, Thompson TE (1990) Interaction of cholesterol with various glycerophospholipids and sphingomyelin. Biochemistry 29:10670–10675PubMedCrossRefGoogle Scholar
  25. 25.
    Schroeder R, London E, Brown D (1994) Interactions between saturated acyl chains confer detergent resistance on lipids and glycosylphosphatidylinositol (GPI)-anchored proteins: GPI-anchored proteins in liposomes and cells show similar behavior. Proc Natl Acad Sci USA 91:12130–12134PubMedCrossRefGoogle Scholar
  26. 26.
    Rodgers W, Crise B, Rose JK (1994) Signals determining protein tyrosine kinase and glycosyl-phosphatidylinositol-anchored protein targeting to a glycolipid-enriched membrane fraction. Mol Cell Biol 14:5384–5391PubMedGoogle Scholar
  27. 27.
    Heerklotz H (2002) Triton promotes domain formation in lipid raft mixtures. Biophys J 83:2693–2701PubMedCrossRefGoogle Scholar
  28. 28.
    Munro S (2003) Lipid rafts: elusive or illusive? Cell 115:377–388PubMedCrossRefGoogle Scholar
  29. 29.
    Chichili GR, Rodgers W (2007) Clustering of membrane raft proteins by the actin cytoskeleton. J Biol Chem 282:36682–36691PubMedCrossRefGoogle Scholar
  30. 30.
    Jordan S, Rodgers W (2003) T cell glycolipid-enriched membrane domains are constitutively assembled as membrane patches that translocate to immune synapses. J Immunol 171:78–87PubMedGoogle Scholar
  31. 31.
    Rodgers W, Zavzavadjian J (2001) Glycolipid-enriched membrane domains are assembled into membrane patches by associating with the actin cytoskeleton. Exp Cell Res 267:173–183PubMedCrossRefGoogle Scholar
  32. 32.
    Grakoui A, Bromley SK, Sumen C, Davis MM, Shaw AS, Allen PM, Dustin ML (1999) The immunological synapse: a molecular machine controlling T cell activation. Science 285:221–227PubMedCrossRefGoogle Scholar
  33. 33.
    Golub T, Caroni P (2005) Pi(4, 5)P2-dependent microdomain assemblies capture microtubules to promote and control leading edge motility. J Cell Biol 169:151–165PubMedCrossRefGoogle Scholar
  34. 34.
    Gomez-Mouton C, Abad JL, Mira E, Lacalle RA, Gallardo E, Jimenez-Baranda S, Illa I, Bernad A, Manes S, Martinez AC (2001) Segregation of leading-edge and uropod components into specific lipid rafts during t cell polarization. Proc Natl Acad Sci USA 98:9642–9647PubMedCrossRefGoogle Scholar
  35. 35.
    Gomez-Mouton C, Lacalle RA, Mira E, Jimenez-Baranda S, Barber DF, Carrera AC, Martinez AC, Manes S (2004) Dynamic redistribution of raft domains as an organizing platform for signaling during cell chemotaxis. J Cell Biol 164:759–768PubMedCrossRefGoogle Scholar
  36. 36.
    Gaus K, Le Lay S, Balasubramanian N, Schwartz MA (2006) Integrin-mediated adhesion regulates membrane order. J Cell Biol 174:725–734PubMedCrossRefGoogle Scholar
  37. 37.
    Krauss K, Altevogt P (1999) Integrin leukocyte function-associated antigen-1-mediated cell binding can be activated by clustering of membrane rafts. J Biol Chem 274:36921–36927PubMedCrossRefGoogle Scholar
  38. 38.
    Causeret M, Taulet N, Comunale F, Favard C, Gauthier-Rouviere C (2005) N-cadherin association with lipid rafts regulates its dynamic assembly at cell–cell junctions in C2C12 myoblasts. Mol Biol Cell 16:2168–2180PubMedCrossRefGoogle Scholar
  39. 39.
    Lambert M, Thoumine O, Brevier J, Choquet D, Riveline D, Mege RM (2007) Nucleation and growth of cadherin adhesions. Exp Cell Res 313:4025–4040PubMedCrossRefGoogle Scholar
  40. 40.
    Decker L, ffrench-Constant C (2004) Lipid rafts and integrin activation regulate oligodendrocyte survival. J Neurosci 24:3816–3825PubMedCrossRefGoogle Scholar
  41. 41.
    Porter JC, Hogg N (1998) Integrins take partners: cross-talk between integrins and other membrane receptors. Trends Cell Biol 8:390–396PubMedCrossRefGoogle Scholar
  42. 42.
    Lehembre F, Yilmaz M, Wicki A, Schomber T, Strittmatter K, Ziegler D, Kren A, Went P, Derksen PW, Berns A, Jonkers J, Christofori G (2008) NCAM-induced focal adhesion assembly: a functional switch upon loss of E-cadherin. EMBO J 27:2603–2615PubMedCrossRefGoogle Scholar
  43. 43.
    Plowman SJ, Muncke C, Parton RG, Hancock JF (2005) H-ras, K-ras, and inner plasma membrane raft proteins operate in nanoclusters with differential dependence on the actin cytoskeleton. Proc Natl Acad Sci USA 102:15500–15505PubMedCrossRefGoogle Scholar
  44. 44.
    Tian T, Harding A, Inder K, Plowman S, Parton RG, Hancock JF (2007) Plasma membrane nanoswitches generate high-fidelity ras signal transduction. Nat Cell Biol 9:905–914PubMedCrossRefGoogle Scholar
  45. 45.
    Hammond AT, Heberle FA, Baumgart T, Holowka D, Baird B, Feigenson GW (2005) Crosslinking a lipid raft component triggers liquid ordered-liquid disordered phase separation in model plasma membranes. Proc Natl Acad Sci USA 102:6320–6325PubMedCrossRefGoogle Scholar
  46. 46.
    Forstner MB, Yee CK, Parikh AN, Groves JT (2006) Lipid lateral mobility and membrane phase structure modulation by protein binding. J Am Chem Soc 128:15221–15227PubMedCrossRefGoogle Scholar
  47. 47.
    Tong J, Nguyen L, Vidal A, Simon SA, Skene JH, McIntosh TJ (2008) Role of GAP-43 in sequestering phosphatidylinositol 4, 5-bisphosphate to raft bilayers. Biophys J 94:125–133PubMedCrossRefGoogle Scholar
  48. 48.
    Douglass AD, Vale RD (2005) Single-molecule microscopy reveals plasma membrane microdomains created by protein–protein networks that exclude or trap signaling molecules in T cells. Cell 121:937–950PubMedCrossRefGoogle Scholar
  49. 49.
    Nebl T, Pestonjamasp KN, Leszyk JD, Crowley JL, Oh SW, Luna EJ (2002) Proteomic analysis of a detergent-resistant membrane skeleton from neutrophil plasma membranes. J Biol Chem 277:43399–43409PubMedCrossRefGoogle Scholar
  50. 50.
    Bini L, Pacini S, Liberatori S, Valensin S, Pellegrini M, Raggiaschi R, Pallini V, Baldari CT (2003) Extensive temporally regulated reorganization of the lipid raft proteome following T-cell antigen receptor triggering. Biochem J 369:301–309PubMedCrossRefGoogle Scholar
  51. 51.
    von Haller PD, Donohoe S, Goodlett DR, Aebersold R, Watts JD (2001) Mass spectrometric characterization of proteins extracted from jurkat T cell detergent-resistant membrane domains. Proteomics 1:1010–1021CrossRefGoogle Scholar
  52. 52.
    Yanagida M, Nakayama H, Yoshizaki F, Fujimura T, Takamori K, Ogawa H, Iwabuchi K (2007) Proteomic analysis of plasma membrane lipid rafts of HL-60 cells. Proteomics 7:2398–2409PubMedCrossRefGoogle Scholar
  53. 53.
    Yu MJ, Pisitkun T, Wang G, Aranda JF, Gonzales PA, Tchapyjnikov D, Shen RF, Alonso MA, Knepper MA (2008) Large-scale quantitative LC-MS/MS analysis of detergent-resistant membrane proteins from rat renal collecting duct. Am J Physiol Cell Physiol 295:C661–C678PubMedCrossRefGoogle Scholar
  54. 54.
    MacLellan DL, Steen H, Adam RM, Garlick M, Zurakowski D, Gygi SP, Freeman MR, Solomon KR (2005) A quantitative proteomic analysis of growth factor-induced compositional changes in lipid rafts of human smooth muscle cells. Proteomics 5:4733–4742PubMedCrossRefGoogle Scholar
  55. 55.
    Liu AP, Fletcher DA (2006) Actin polymerization serves as a membrane domain switch in model lipid bilayers. Biophys J 91:4064–4070PubMedCrossRefGoogle Scholar
  56. 56.
    Gaus K, Chklovskaia E, Fazekas de St Groth B, Jessup W, Harder T (2005) Condensation of the plasma membrane at the site of T lymphocyte activation. J Cell Biol 171:121–131PubMedCrossRefGoogle Scholar
  57. 57.
    Kusumi A, Nakada C, Ritchie K, Murase K, Suzuki K, Murakoshi H, Kasai RS, Kondo J, Fujiwara T (2005) Paradigm shift of the plasma membrane concept from the two-dimensional continuum fluid to the partitioned fluid: high-speed single-molecule tracking of membrane molecules. Annu Rev Biophys Biomol Struct 34:351–378PubMedCrossRefGoogle Scholar
  58. 58.
    Suzuki KG, Fujiwara TK, Edidin M, Kusumi A (2007) Dynamic recruitment of phospholipase C γ at transiently immobilized GPI-anchored receptor clusters induces IP3-Ca2+ signaling: single-molecule tracking study 2. J Cell Biol 177:731–742PubMedCrossRefGoogle Scholar
  59. 59.
    Suzuki KG, Fujiwara TK, Sanematsu F, Iino R, Edidin M, Kusumi A (2007) GPI-anchored receptor clusters transiently recruit Lyn and Gα for temporary cluster immobilization and Lyn activation: single-molecule tracking study 1. J Cell Biol 177:717–730PubMedCrossRefGoogle Scholar
  60. 60.
    Hess ST, Gould TJ, Gudheti MV, Maas SA, Mills KD, Zimmerberg J (2007) Dynamic clustered distribution of hemagglutinin resolved at 40 nm in living cell membranes discriminates between raft theories. Proc Natl Acad Sci USA 104:17370–17375PubMedCrossRefGoogle Scholar
  61. 61.
    Roumier A, Olivo-Marin JC, Arpin M, Michel F, Martin M, Mangeat P, Acuto O, Dautry-Varsat A, Alcover A (2001) The membrane-microfilament linker ezrin is involved in the formation of the immunological synapse and in T cell activation. Immunity 15:715–728PubMedCrossRefGoogle Scholar
  62. 62.
    Allenspach EJ, Cullinan P, Tong J, Tang Q, Tesciuba AG, Cannon JL, Takahashi SM, Morgan R, Burkhardt JK, Sperling AI (2001) ERM-dependent movement of CD43 defines a novel protein complex distal to the immunological synapse. Immunity 15:739–750PubMedCrossRefGoogle Scholar
  63. 63.
    Lee JL, Wang MJ, Sudhir PR, Chen JY (2008) CD44 engagement promotes matrix-derived survival through the CD44-Src-integrin axis in lipid rafts. Mol Cell Biol 28:5710–5723PubMedCrossRefGoogle Scholar
  64. 64.
    Balasubramanian N, Scott DW, Castle JD, Casanova JE, Schwartz MA (2007) Arf6 and microtubules in adhesion-dependent trafficking of lipid rafts. Nat Cell Biol 9:1381–1391PubMedCrossRefGoogle Scholar
  65. 65.
    Czech MP (2000) PIP2 and PIP3: Complex roles at the cell surface. Cell 100:603–606PubMedCrossRefGoogle Scholar
  66. 66.
    Yin HL, Janmey PA (2003) Phosphoinositide regulation of the actin cytoskeleton. Annu Rev Physiol 65:761–789PubMedCrossRefGoogle Scholar
  67. 67.
    Varnai P, Balla T (1998) Visualization of phosphoinositides that bind pleckstrin homology domains: Calcium- and agonist-induced dynamic changes and relationship to myo-[3H]inositol-labeled phosphoinositide pools. J Cell Biol 143:501–510PubMedCrossRefGoogle Scholar
  68. 68.
    Harlan JE, Hajduk PJ, Yoon HS, Fesik SW (1994) Pleckstrin homology domains bind to phosphatidylinositol-4, 5-bisphosphate. Nature 371:168–170PubMedCrossRefGoogle Scholar
  69. 69.
    Lemon G, Gibson WG, Bennett MR (2003) Metabotropic receptor activation, desensitization and sequestration-II: modelling the dynamics of the pleckstrin homology domain. J Theor Biol 223:113–129PubMedCrossRefGoogle Scholar
  70. 70.
    Hirao M, Sato N, Kondo T, Yonemura S, Monden M, Sasaki T, Takai Y, Tsukita S, Tsukita S (1996) Regulation mechanism of ERM (ezrin/radixin/moesin) protein/plasma membrane association: possible involvement of phosphatidylinositol turnover and Rho-dependent signaling pathway. J Cell Biol 135:37–51PubMedCrossRefGoogle Scholar
  71. 71.
    Heiska L, Alfthan K, Gronholm M, Vilja P, Vaheri A, Carpen O (1998) Association of ezrin with intercellular adhesion molecule-1 and -2 (ICAM-1 and ICAM-2). Regulation by phosphatidylinositol 4, 5-bisphosphate. J Biol Chem 273:21893–21900PubMedCrossRefGoogle Scholar
  72. 72.
    Blin G, Margeat E, Carvalho K, Royer CA, Roy C, Picart C (2008) Quantitative analysis of the binding of ezrin to large unilamellar vesicles containing phosphatidylinositol 4, 5 bisphosphate. Biophys J 94:1021–1033PubMedCrossRefGoogle Scholar
  73. 73.
    Zhang M, Bohlson SS, Dy M, Tenner AJ (2005) Modulated interaction of the ERM protein, moesin, with CD93. Immunology 115:63–73PubMedCrossRefGoogle Scholar
  74. 74.
    Kaufmann S, Kas J, Goldmann WH, Sackmann E, Isenberg G (1992) Talin anchors and nucleates actin filaments at lipid membranes. A direct demonstration. FEBS Lett 314:203–205PubMedCrossRefGoogle Scholar
  75. 75.
    Martel V, Racaud-Sultan C, Dupe S, Marie C, Paulhe F, Galmiche A, Block MR, Albiges-Rizo C (2001) Conformation, localization, and integrin binding of talin depend on its interaction with phosphoinositides. J Biol Chem 276:21217–21227PubMedCrossRefGoogle Scholar
  76. 76.
    Villalba M, Bi K, Rodriguez F, Tanaka Y, Schoenberger S, Altman A (2001) Vav1/Rac-dependent actin cytoskeleton reorganization is required for lipid raft clustering in T cells. J Cell Biol 155:331–338PubMedCrossRefGoogle Scholar
  77. 77.
    Inabe K, Ishiai M, Scharenberg AM, Freshney N, Downward J, Kurosaki T (2002) Vav3 modulates B cell receptor responses by regulating phosphoinositide 3-kinase activation. J Exp Med 195:189–200PubMedCrossRefGoogle Scholar
  78. 78.
    Bustelo XR (2000) Regulatory and signaling properties of the Vav family. Mol Cell Biol 20:1461–1477PubMedCrossRefGoogle Scholar
  79. 79.
    Higgs HN, Pollard TD (2000) Activation by Cdc42 and PiP2 of Wiskott–Aldrich syndrome protein (WASp) stimulates actin nucleation by Arp2/3 complex. J Cell Biol 150:1311–1320PubMedCrossRefGoogle Scholar
  80. 80.
    Rozelle AL, Machesky LM, Yamamoto M, Driessens MH, Insall RH, Roth MG, Luby-Phelps K, Marriott G, Hall A, Yin HL (2000) Phosphatidylinositol 4, 5-bisphosphate induces actin-based movement of raft-enriched vesicles through WASp–Arp2/3. Curr Biol 10:311–320PubMedCrossRefGoogle Scholar
  81. 81.
    Lai FP, Szczodrak M, Block J, Faix J, Breitsprecher D, Mannherz HG, Stradal TE, Dunn GA, Small JV, Rottner K (2008) Arp2/3 complex interactions and actin network turnover in lamellipodia. EMBO J 27:982–992PubMedCrossRefGoogle Scholar
  82. 82.
    Goley ED, Welch MD (2006) The Arp2/3 complex: an actin nucleator comes of age. Nat Rev Mol Cell Biol 7:713–726PubMedCrossRefGoogle Scholar
  83. 83.
    Tseng Y, Wirtz D (2004) Dendritic branching and homogenization of actin networks mediated by Arp2/3 complex. Phys Rev Lett 93:258104PubMedCrossRefGoogle Scholar
  84. 84.
    Hope HR, Pike LJ (1996) Phosphoinositides and phosphoinositide-utilizing enzymes in detergent-insoluble lipid domains. Mol Biol Cell 7:843–851PubMedGoogle Scholar
  85. 85.
    Laux T, Fukami K, Thelen M, Golub T, Frey D, Caroni P (2000) GAP43, MARCKS, and CAP23 modulate PI(4, 5)P2 at plasmalemmal rafts, and regulate cell cortex actin dynamics through a common mechanism. J Cell Biol 149:1455–1472PubMedCrossRefGoogle Scholar
  86. 86.
    Parmryd I, Adler J, Patel R, Magee AI (2003) Imaging metabolism of phosphatidylinositol 4, 5-bisphosphate in T-cell GM1-enriched domains containing ras proteins. Exp Cell Res 285:27–38PubMedCrossRefGoogle Scholar
  87. 87.
    van Rheenen J, Achame EM, Janssen H, Calafat J, Jalink K (2005) PIP2 signaling in lipid domains: a critical re-evaluation. EMBO J 24:1664–1673PubMedCrossRefGoogle Scholar
  88. 88.
    Johnson CM, Chichili GR, Rodgers W (2008) Compartmentalization of phosphatidylinositol 4, 5-bisphosphate signaling evidenced using targeted phosphatases. J Biol Chem 283:29920–29928PubMedCrossRefGoogle Scholar
  89. 89.
    Charras CT, Hu CK, Coughlin M, Mitchison TJ (2006) Reassembly of contractile actin cortex in cell blebs. J Cell Biol 175:477–490PubMedCrossRefGoogle Scholar
  90. 90.
    Arrieumerlou C, Randriamampita C, Bismuth G, Trautmann A (2000) Rac is involved in early TCR signaling. J. Immunol 165:3182–3189PubMedGoogle Scholar
  91. 91.
    Zhang W, Trible RP, Samelson LE (1998) LAT palmitoylation: its essential role in membrane microdomain targeting and tyrosine phosphorylation during T cell activation. Immunity 9:239–246PubMedCrossRefGoogle Scholar
  92. 92.
    Brdicka T, Pavlistova D, Leo A, Bruyns E, Korinek V, Angelisova P, Scherer J, Shevchenko A, Hilgert I, Cerny J, Drbal K, Kuramitsu Y, Kornacker B, Horejsi V, Schraven B (2000) Phosphoprotein associated with glycosphingolipid-enriched microdomains (PAG), a novel ubiquitously expressed transmembrane adaptor protein, binds the protein tyrosine kinase Csk and is involved in regulation of T cell activation. J Exp Med 191:1591–1604PubMedCrossRefGoogle Scholar
  93. 93.
    Roy S, Luetterforst R, Harding A, Apolloni A, Etheridge M, Stang E, Rolls B, Hancock JF, Parton RG (1999) Dominant-negative caveolin inhibits H-ras function by disrupting cholesterol-rich plasma membrane domains. Nat Cell Biol 1:98–105PubMedCrossRefGoogle Scholar
  94. 94.
    Viola A, Schroeder S, Sakakibara Y, Lanzavecchia A (1999) T lymphocyte costimulation mediated by reorganization of membrane microdomains. Science 283:680–682PubMedCrossRefGoogle Scholar
  95. 95.
    Xavier R, Brennan T, Li Q, McCormack C, Seed B (1998) Membrane compartmentation is required for efficient T cell activation. Immunity 8:723–732PubMedCrossRefGoogle Scholar
  96. 96.
    Kabouridis PS, Magee AI, Ley SC (1997) S-acylation of Lck protein tyrosine kinase is essential for its signalling function in T lymphocytes. EMBO J 16:4983–4998PubMedCrossRefGoogle Scholar
  97. 97.
    Bunnell SC, Kapoor V, Trible RP, Zhang W, Samelson LE (2001) Dynamic actin polymerization drives T cell receptor-induced spreading: A role for the signal transduction adaptor LAT. Immunity 14:315–329PubMedCrossRefGoogle Scholar
  98. 98.
    Barda-Saad M, Braiman A, Titerence R, Bunnell SC, Barr VA, Samelson LE (2005) Dynamic molecular interactions linking the T cell antigen receptor to the actin cytoskeleton. Nat Immunol 6:80–89PubMedCrossRefGoogle Scholar
  99. 99.
    Gomez TS, Billadeau DD (2008) T cell activation and the cytoskeleton: you can’t have one without the other. Adv Immunol 97:1–64PubMedCrossRefGoogle Scholar
  100. 100.
    Sah VP, Seasholtz TM, Sagi SA, Brown JH (2000) The role of Rho in G protein-coupled receptor signal transduction. Annu Rev Pharmacol Toxicol 40:459–489PubMedCrossRefGoogle Scholar
  101. 101.
    Pullikuth AK, Catling AD (2007) Scaffold mediated regulation of MAPK signaling and cytoskeletal dynamics: A perspective. Cell Signal 19:1621–1632PubMedCrossRefGoogle Scholar
  102. 102.
    Rodgers W, Rose JK (1996) Exclusion of CD45 inhibits activity of p56Lck associated with glycolipid-enriched membrane domains. J Cell Biol 135:1515–1523PubMedCrossRefGoogle Scholar
  103. 103.
    Davidson D, Bakinowski M, Thomas ML, Horejsi V, Veillette A (2003) Phosphorylation-dependent regulation of T-cell activation by PAG/Cbp, a lipid raft-associated transmembrane adaptor. Mol Cell Biol 23:2017–2028PubMedCrossRefGoogle Scholar
  104. 104.
    Freiberg BA, Kupfer H, Maslanik W, Delli J, Kappler J, Zaller DM, Kupfer A (2002) Staging and resetting T cell activation in SMACs. Nat Immunol 3:911–917PubMedCrossRefGoogle Scholar
  105. 105.
    Miceli MC, Moran M, Chung CD, Patel VP, Low T, Zinnanti W (2001) Co-stimulation and counter-stimulation: lipid raft clustering controls TCR signaling and functional outcomes. Semin Immunol 13:115–128PubMedCrossRefGoogle Scholar
  106. 106.
    Wulfing C, Purtic B, Klem J, Schatzle JD (2003) Stepwise cytoskeletal polarization as a series of checkpoints in innate but not adaptive cytolytic killing. Proc Natl Acad Sci USA 100:7767–7772PubMedCrossRefGoogle Scholar
  107. 107.
    Montixi C, Langlet C, Bernard AM, Thimonier J, Dubois C, Wurbel MA, Chauvin JP, Pierres M, He HT (1998) Engagement of T cell receptor triggers its recruitment to low-density detergent-insoluble membrane domains. EMBO J 17:5334–5348PubMedCrossRefGoogle Scholar
  108. 108.
    Janes PW, Ley SC, Magee AI (1999) Aggregation of lipid rafts accompanies signaling via the T cell antigen receptor. J Cell Biol 147:447–461PubMedCrossRefGoogle Scholar
  109. 109.
    Tavano R, Contento RL, Baranda SJ, Soligo M, Tuosto L, Manes S, Viola A (2006) CD28 interaction with filamin-A controls lipid raft accumulation at the T-cell immunological synapse. Nat Cell Biol 8:1270–1276PubMedCrossRefGoogle Scholar
  110. 110.
    Tavano R, Gri G, Molon B, Marinari B, Rudd CE, Tuosto L, Viola A (2004) CD28 and lipid rafts coordinate recruitment of Lck to the immunological synapse of human T lymphocytes. J Immunol 173:5392–5397PubMedGoogle Scholar
  111. 111.
    Cemerski S, Das J, Giurisato E, Markiewicz MA, Allen PM, Chakraborty AK, Shaw AS (2008) The balance between T cell receptor signaling and degradation at the center of the immunological synapse is determined by antigen quality. Immunity 29:414–422PubMedCrossRefGoogle Scholar
  112. 112.
    Lee KH, Holdorf AD, Dustin ML, Chan AC, Allen PM, Shaw AS (2002) T cell receptor signaling precedes immunological synapse formation. Science 295:1539–1542PubMedCrossRefGoogle Scholar
  113. 113.
    Rentero C, Zech T, Quinn CM, Engelhardt K, Williamson D, Grewal T, Jessup W, Harder T, Gaus K (2008) Functional implications of plasma membrane condensation for T cell activation. PLoS ONE 3:e2262PubMedCrossRefGoogle Scholar
  114. 114.
    Kovacs B, Parry RV, Ma Z, Fan E, Shivers DK, Freiberg BA, Thomas AK, Rutherford R, Rumbley CA, Riley JL, Finkel TH (2005) Ligation of CD28 by its natural ligand CD86 in the absence of TCR stimulation induces lipid raft polarization in human CD4 T cells. J Immunol 175:7848–7854PubMedGoogle Scholar
  115. 115.
    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 162:1367–1375PubMedGoogle Scholar
  116. 116.
    Yang H, Reinherz EL (2001) Dynamic recruitment of human CD2 into lipid rafts. Linkage to T cell signal transduction. J Biol Chem 276:18775–18785PubMedCrossRefGoogle Scholar
  117. 117.
    Revy P, Sospedra M, Barbour B, Trautmann A (2001) Functional antigen-independent synapses formed between T cells and dendritic cells. Nat Immunol 2:925–931PubMedCrossRefGoogle Scholar
  118. 118.
    Salomon B, Bluestone JA (2001) Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation. Annu Rev Immunol 19:225–252PubMedCrossRefGoogle Scholar
  119. 119.
    Schneider H, Cai YC, Cefai D, Raab M, Rudd CE (1995) Mechanisms of CD28 signalling. Res Immunol 146:149–154PubMedCrossRefGoogle Scholar
  120. 120.
    Raab M, Cai YC, Bunnell SC, Heyeck SD, Berg LJ, Rudd CE (1995) p56Lck and p59Fyn regulate CD28 binding to phosphatidylinositol 3-kinase, growth factor receptor-bound protein GRB-2, and T cell-specific protein-tyrosine kinase ITK: implications for T-cell costimulation. Proc Natl Acad Sci USA 92:8891–8895PubMedCrossRefGoogle Scholar
  121. 121.
    Holdorf AD, Green JM, Levin SD, Denny MF, Straus DB, Link V, Changelian PS, Allen PM, Shaw AS (1999) Proline residues in CD28 and the Src homology (SH)3 domain of Lck are required for T cell costimulation. J Exp Med 190:375–384PubMedCrossRefGoogle Scholar
  122. 122.
    Andres PG, Howland KC, Dresnek D, Edmondson S, Abbas AK, Krummel MF (2004) CD28 signals in the immature immunological synapse. J Immunol 172:5880–5886PubMedGoogle Scholar
  123. 123.
    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 27:76–88PubMedCrossRefGoogle Scholar
  124. 124.
    Bunnell SC, Hong DI, Kardon JR, Yamazaki T, McGlade CJ, Barr VA, Samelson LE (2002) T cell receptor ligation induces the formation of dynamically regulated signaling assemblies. J Cell Biol 158:1263–1275PubMedCrossRefGoogle Scholar
  125. 125.
    Van Komen JS, Mishra S, Byrum J, Chichili GR, Yaciuk JC, Farris AD, Rodgers W (2007) Early and dynamic polarization of T cell membrane rafts and constituents prior to TCR stop signals. J Immunol 179:6845–6855PubMedGoogle Scholar
  126. 126.
    Bagatolli LA, Gratton E, Fidelio GD (1998) Water dynamics in glycosphingolipid aggregates studied by laurdan fluorescence. Biophys J 75:331–341PubMedCrossRefGoogle Scholar
  127. 127.
    Bagatolli LA, Gratton E (2000) A correlation between lipid domain shape and binary phospholipid mixture composition in free standing bilayers: a two-photon fluorescence microscopy study. Biophys J 79:434–447PubMedCrossRefGoogle Scholar
  128. 128.
    Gaus K, Gratton E, Kable EP, Jones AS, Gelissen I, Kritharides L, Jessup W (2003) Visualizing lipid structure and raft domains in living cells with two-photon microscopy. Proc Natl Acad Sci USA 100:15554–15559PubMedCrossRefGoogle Scholar
  129. 129.
    Goswami D, Gowrishankar K, Bilgrami S, Ghosh S, Raghupathy R, Chadda R, Vishwakarma R, Rao M, Mayor S (2008) Nanoclusters of GPI-anchored proteins are formed by cortical actin-driven activity. Cell 135:1085–1097PubMedCrossRefGoogle Scholar

Copyright information

© Birkhäuser Verlag, Basel/Switzerland 2009

Authors and Affiliations

  1. 1.Cardiovascular Biology Research ProgramOklahoma Medical Research FoundationOklahoma CityUSA

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