Spatio-Temporal Signaling in Mast Cells

  • Bridget S. Wilson
  • Janet M. Oliver
  • Diane S. Lidke
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 716)

Abstract

This chapter summarizes the evidence for localized signaling domains in mast cells and basophils, with a particular focus on the high affinity IgE receptor, FcεRI and its crosstalk with other membrane proteins. It is noteworthy that a literature spanning 30 years established the FcεRI as a model receptor for studying activation-induced changes in receptor diffusion and lipid raft association. Now a combination of high resolution microscopy methods, including immunoelectron microscopy and sophisticated fluorescence-based techniques, provide new insight into the nanoscale spatial and temporal aspects of receptor topography on the mast cell plasma membrane. Physical crosslinking of FcεRI with multivalent ligands leads to formation of IgE receptor clusters, termed “signaling patches,” that recruit downstream signaling molecules. However, classes of receptors that engage solely withmono valent ligands can also form distinctive signaling patches. The dynamic relationships between receptor diffusion, aggregation state, clustering, signal initiation and signal strength are discussed in the context of these recent findings.

Keywords

Mast Cell Lipid Raft Bivalent Ligand Signaling Patch Mast Cell Membrane 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Wasserman SI. Basic mechanisms in asthma. Ann Allergy 1988; 60(5):477–482.PubMedGoogle Scholar
  2. 2.
    Gilmartin L, Tarleton CA, Schuyler M et al. A comparison of inflammatory mediators released by basophils of asthmatic and control subjects in response to high-affinity IgE receptor aggregation. Int Arch Allergy Immunol 2008; 145(3):182–192.PubMedCrossRefGoogle Scholar
  3. 3.
    Gilfillan AM, Rivera J. The tyrosine kinase network regulating mast cell activation. Immunol Rev 2009; 228(1):149–169.PubMedCrossRefGoogle Scholar
  4. 4.
    Schlessinger J, Metzger H, Webb WW et al. Lateral motion and valence of Fc receptors on rat peritoneal mast-cells. Biophys J 1977; 17 (2):A72–A72.Google Scholar
  5. 5.
    Mccloskey MA, Liu ZY, Poo MM. Lateral electromigration and diffusion of Fc-epsilon receptors on rat basophilic leukemia-cells—effects of IgE binding. J Cell Biol 1984; 99(3):778–787.CrossRefGoogle Scholar
  6. 6.
    Zidovetzki R, Bartholdi M, Arndtjovin D et al. Rotational-dynamics of the Fc receptor for immunoglobulin-e on histamine-releasing rat basophilic leukemia-cells. Biochemistry 1986; 25(15):4397–4401.PubMedCrossRefGoogle Scholar
  7. 7.
    Pecht I, Ortega E, Jovin TM. Rotational-dynamics of the Fc-epsilon receptor on mast-cells monitored by specific monoclonal-antibodies and IgE. Biochemistry 1991; 30(14):3450–3458.PubMedCrossRefGoogle Scholar
  8. 8.
    Myers JN, Holowka D, Baird B. Rotational motion of monomeric and dimeric immunoglobulin E-receptor complexes. Biochemistry 1992; 31(2):567–575.PubMedCrossRefGoogle Scholar
  9. 9.
    Ryan TA, Myers J, Holowka D et al. Molecular crowding on the cell surface. Science 1988; 239(4835):61–64.PubMedCrossRefGoogle Scholar
  10. 10.
    Feder TJ, BrustMascher I, Slattery JP et al. Constrained diffusion or immobile fraction on cell surfaces: Anew interpretation. Biophys J 1996; 70(6):2767–2773.PubMedCrossRefGoogle Scholar
  11. 11.
    Menon AK, Holowka D, Webb WW et al. Cross-linking of receptor-bound IgE to aggregates larger than dimers leads to rapid immobilization. J Cell Biol 1986; 102(2):541–550.PubMedCrossRefGoogle Scholar
  12. 12.
    Tamir I, SchweitzerStenner R, Pecht I. Immobilization of the type I receptor for IgE initiates signal transduction in mast cells. Biochemistry 1996; 35(21):6872–6883.PubMedCrossRefGoogle Scholar
  13. 13.
    Holowka D, Sil D, Torigoe C et al. Insights into immunoglobulin E receptor signaling from structurally defined ligands. Immunol Rev 2007; 217:269–279.PubMedCrossRefGoogle Scholar
  14. 14.
    Singer SJ, Nicolson GL. The fluid mosaic model of the structure of cell membranes. Science 1972; 175(23):720–731.PubMedCrossRefGoogle Scholar
  15. 15.
    Brown DA, Rose JK. Sorting of gpi-anchored proteins to glycolipid-enriched membrane subdomains during transport to the apical cell-surface. Cell 1992; 68(3):533–544.PubMedCrossRefGoogle Scholar
  16. 16.
    Simons K, Ikonen E. Functional rafts in cell membranes. Nature 1997; 387(6633):569–572.PubMedCrossRefGoogle Scholar
  17. 17.
    Ahmed SN, Brown DA, London E. On the origin of sphingolipid/cholesterol-rich detergent-insoluble cell membranes: Physiological concentrations of cholesterol and sphingolipid induce formation of a detergent-insoluble, liquid-ordered lipid phase in model membranes. Biochemistry 1997; 36(36): 10944–10953.PubMedCrossRefGoogle Scholar
  18. 18.
    Field KA, Holowka D, Baird B. Fc-epsilon-ri-mediated recruitment of P53/56 (Lyn) to detergent-resistant membrane domains accompanies cellular signaling. Proc Natl Acad Sci USA 1995; 92(20):9201–9205.PubMedCrossRefGoogle Scholar
  19. 19.
    Field KA, Holowka D, Baird B. Compartmentalized activation of the high affinity immunoglobulin E receptor within membrane domains. J Biol Chem 1997; 272(7):4276–4280.PubMedCrossRefGoogle Scholar
  20. 20.
    Field KA, Holowka D, Baird B. Structural aspects of the association of Fc epsilon RI with detergent-resistant membranes. J Biol Chem 1999; 274(3): 1753–1758.PubMedCrossRefGoogle Scholar
  21. 21.
    Draberova L, Draber P. Thy-1 glycoprotein and src-like protein-tyrosine kinase P53/P56 (Lyn) are associated in large detergent-resistant complexes in rat basophilic leukemia-cells. Proc Natl Acad Sci USA 1993; 90(8):3611–3615.PubMedCrossRefGoogle Scholar
  22. 22.
    Vereb G, Szollosi J, Matko J et al. Dynamic, yet structured: the cell membrane three decades after the singer-nicolson model. Proc Natl Acad Sci USA 2003; 100(14):8053–8058.PubMedCrossRefGoogle Scholar
  23. 23.
    Lagerholm BC, Weinreb GE, Jacobson K et al. Detecting microdomains in intact cell membranes. Annu Rev Phys Chem 2005; 56:309–336.PubMedCrossRefGoogle Scholar
  24. 24.
    Hancock JF. Lipidrafts: contentious only from simplistic standpoints. Nat Rev Mol Cell Biol 2006; 7(6):456–462.PubMedCrossRefGoogle Scholar
  25. 25.
    Jacobson K, Mouritsen OG, Anderson RG. Lipid rafts: at a crossroad between cell biology and physics. Nat Cell Biol 2007; 9(1):7–14.PubMedCrossRefGoogle Scholar
  26. 26.
    Lillemeier BF, Pfeiffer JR, Surviladze Z et al. Plasma membrane-associated proteins are clustered into islands attached to the cytoskeleton. Proc Natl Acad Sci USA 2006; 103(50): 18992–18997.PubMedCrossRefGoogle Scholar
  27. 27.
    Lillemeier BF, Mortelmaier MA, Forstner MB et al. TCR and Lat are expressed on separate protein islands on T-cell membranes and concatenate during activation (vol 11, pg 90, 2010). Nat Immunol 2010; 11(6):543–543.CrossRefGoogle Scholar
  28. 28.
    Yechiel E, Edidin M. Micrometer-scale domains in fibroblast plasma-membranes. J Cell Biol 1987; 105(2):755–760.PubMedCrossRefGoogle Scholar
  29. 29.
    Thomas JL, Feder TJ, Webb WW. Effects of protein-concentration on ige receptor mobility in rat basophilic leukemia-cell plasma-membranes. Biophys J 1992; 61(5): 1402–1412.PubMedCrossRefGoogle Scholar
  30. 30.
    Douglass AD, Vale RD. Single-molecule microscopy reveals plasma membrane microdomains created by protein-protein networks that exclude or trap signaling molecules in T-cells. Cell 2005; 121(6):937–950.PubMedCrossRefGoogle Scholar
  31. 31.
    Stump RF, Pfeiffer JR, Seagrave J et al. Mapping gold-labeled ige receptors on mast-cells by scanning electron-microscopy—receptor distributions revealed by silver enhancement, backscattered electron imaging and digital image-analysis. J Histochem Cytochem 1988; 36(5):493–502.PubMedCrossRefGoogle Scholar
  32. 32.
    Seagrave J, Pfeiffer JR, Wofsy C et al. Relationship of ige receptor topography to secretion in Rbl-2h3 mast-cells. J Cell Physiol 1991; 148(1):139–151.PubMedCrossRefGoogle Scholar
  33. 33.
    Wilson BS, Pfeiffer JR, Oliver JM. Observing FcepsilonRI signaling from the inside of the mast cell membrane. J Cell Biol 2000; 149(5):1131–1142.PubMedCrossRefGoogle Scholar
  34. 34.
    Andrews NL, Lidke KA, Pfeiffer JR et al. Actin restricts Fc epsilon RI diffusion and facilitates antigen-induced receptor immobilization. Nat Cell Biol 2008; 10(8):955–963.PubMedCrossRefGoogle Scholar
  35. 35.
    Andrews NL, Pfeiffer JR, Martinez AM et al. Small, mobile Fc epsilon R1 receptor aggregates are signaling competent. Immunity 2009; 31(3):469–479.PubMedCrossRefGoogle Scholar
  36. 36.
    Lara M, Ortega E, Pecht I et al. Overcoming the signaling defect of Lyn-sequestering, signal-curtailing FcepsilonRI dimers: aggregated dimers can dissociate from Lyn and form signaling complexes with Syk. J Immunol 2001; 167(8):4329–4337.PubMedGoogle Scholar
  37. 37.
    Fattakhova G, Masilamani M, Borrego F et al. The high-affinity immunoglobulin-E receptor (Fc epsilon RI) is endocytosedby an AP-2/clathrin-independent, dynamin-dependent mechanism. Traffic 2006; 7(6):673–685.PubMedCrossRefGoogle Scholar
  38. 38.
    Stoddart A, Jackson AP, Brodsky FM. Plasticity of B-cell receptor internalization upon conditional depletion of clathrin. Mol Biol Cell 2005; 16(5):2339–2348.PubMedCrossRefGoogle Scholar
  39. 39.
    Xue M, Hsieh G, Raymond-Stintz MA et al. Activated N-formyl peptide receptor and high-affinity IgE receptor occupy common domains for signaling and internalization. Mol Biol Cell 2007; 18(4): 1410–1420.PubMedCrossRefGoogle Scholar
  40. 40.
    Barisas BG, Smith SM, Liu JJ et al. Compartmentalization of the Type I Fc epsilon receptor and MAFA on mast cell membranes. Biophys Chem 2007; 126(1–3):209–217.PubMedCrossRefGoogle Scholar
  41. 41.
    Nagy P, Jenei A, Kirsch AK et al. Activation-dependent clustering of the erbB2 receptor tyrosine kinase detected by scanning near-field optical microscopy. J Cell Sci 1999; 112(Pt 11): 1733–1741.PubMedGoogle Scholar
  42. 42.
    Yang S, Raymond-Stintz MA, Ying W et al. Mapping ErbB receptors on breast cancer cell membranes during signal transduction. J Cell Sci 2007; 120(Pt 16):2763–2773.PubMedCrossRefGoogle Scholar
  43. 43.
    Hsieh G, Yang S, Raymond-Stintz M et al. Stochastic simulations of ErbB homo and hetero-dimerization: potential impacts of receptor conformational Ctate and spatial segregation. IET Systems Biology 2008; Invited submission(q-Bio Special issue).Google Scholar
  44. 44.
    Tank DW, Wu ES, Webb WW. Enhanced molecular diffusibility in muscle membrane blebs—release of lateral constraints. J Cell Biol 1982; 92(1):207–212.PubMedCrossRefGoogle Scholar
  45. 45.
    Peters R, Cherry RJ. Lateral and rotational diffusion of bacteriorhodopsin in lipid bilayers—experimental test of the saffman-delbruck equations. Proc Natl Acad Sci USA-Biological Sciences 1982; 79(14):4317–4321.CrossRefGoogle Scholar
  46. 46.
    Menon AK, Holowka D, Webb WW et al. Clustering, mobility and triggering activity of small ligomers of immunoglobulin-E on rat basophilic leukemia-cells. J Cell Biol 1986; 102(2):534–540.PubMedCrossRefGoogle Scholar
  47. 47.
    Posner RG, Subramanian K, Goldstein B et al. Simultaneous cross-linking by 2 nontriggering bivalent ligands causes synergistic signaling of ige Fc-epsilon-Ri complexes. J Immunol 1995; 155(7):3601–3609.PubMedGoogle Scholar
  48. 48.
    Posner RG, Geng D, Haymore S et al. Trivalent antigens for degranulation of mast cells. Org Lett 2007; 9(18):3551–3554.PubMedCrossRefGoogle Scholar
  49. 49.
    Baird EJ, Holowka D, Coates GW et al. Highly effective poly(ethylene glycol) architectures for specific inhibition of immune receptor activation. Biochemistry 2003; 42(44): 12739–12748.PubMedCrossRefGoogle Scholar
  50. 50.
    Mcconnell HM, Watts TH, Weis RM et al. Supported planar membranes in studies of cell-cell recognition in the immune-system. Biochim Biophys Acta 1986; 864(1):95–106.PubMedGoogle Scholar
  51. 51.
    Mccloskey MA, Poo M. Contact-induced redistribution of specific membrane-components—local accumulation and development of adhesion. J Cell Biol 1986; 102(6):2185–2196.PubMedCrossRefGoogle Scholar
  52. 52.
    Carroll-Portillo A, Spendier K, Pfeiffer J et al. Formation of a mast cell synapse: Fc epsilon RI membrane dynamics upon binding mobile or immobilized ligands on surfaces. J Immunol 2010; 184(3): 1328–1338.PubMedCrossRefGoogle Scholar
  53. 53.
    Kepley CL, Wilson BS, Oliver JM. Identification of the Fc epsilon RI-activated tyrosine kinases lyn, syk and zap-70 in human basophils. J Allergy Clin Immunol 1998; 102(2):304–315.PubMedCrossRefGoogle Scholar
  54. 54.
    Sheetz MP. Membrane skeletal dynamics—role in modulation of red-cell deformability, mobility of transmembrane proteins and shape. Semin Hematol 1983; 20(3):175–188.PubMedGoogle Scholar
  55. 55.
    Saxton MJ. Single-particle tracking—effects of corrals. Biophys J 1995; 69(2):389–398.PubMedCrossRefGoogle Scholar
  56. 56.
    Kusumi A, Ike H, Nakada C et al. Single-molecule tracking of membrane molecules: plasma membrane compartmentalization and dynamic assembly of raft-philic signaling molecules. Semin Immunol 2005; 17(1):3–21.PubMedCrossRefGoogle Scholar
  57. 57.
    Wilson BS, Pfeiffer JR, Surviladze Z et al. High resolution mapping of mast cell membranes reveals primary and secondary domains of Fc(epsilon)RI and LAT. J Cell Biol 2001; 154(3):645–658.PubMedCrossRefGoogle Scholar
  58. 58.
    Frankel DJ, Pfeiffer JR, Surviladze Z et al. Revealing the topography of cellular membrane domains by combined atomic force microscopy/fluorescence imaging. Biophys J 2006; 90(7):2404–2413.PubMedCrossRefGoogle Scholar
  59. 59.
    Fujiwara T, Ritchie K, Murakoshi H et al. Phospholipids undergo hop diffusion in compartmentalized cell membrane. J Cell Biol 2002; 157(6):1071–1081.PubMedCrossRefGoogle Scholar
  60. 60.
    Pierini L, Harris NT, Holowka D et al. Evidence supporting a role for microfilaments in regulating the coupling between poorly dissociable IgE-Fc epsilon RI aggregates and downstream signaling pathways. Biochemistry 1997; 36(24):7447–7456.PubMedCrossRefGoogle Scholar
  61. 61.
    Seagrave J, Oliver JM. Antigen-dependent transition of ige to a detergent-insoluble form is associated with reduced ige receptor-dependent secretion from Rbl-2h3 mast-cells. J Cell Physiol 1990; 144(1): 128–136.PubMedCrossRefGoogle Scholar
  62. 62.
    Zhang J, Leiderman K, Pfeiffer JR et al. Characterizing the topography of membrane receptors and signaling molecules from spatial patterns obtained using nanometer-scale electron-dense probes and electron microscopy. Micron 2006; 37(1): 14–34.PubMedCrossRefGoogle Scholar
  63. 63.
    Nag A, Monine MI, Faeder JR et al. Aggregation of membrane proteins by cytosolic cross-linkers: theory and simulation of the LAT-Grb2-SOS1 system. Biophys J 2009; 96(7):2604–2623.PubMedCrossRefGoogle Scholar
  64. 64.
    Bunnell SC, Singer AL, Hong DI et al. Persistence of cooperatively stabilized signaling clusters drives T-cell activation. Mol Cell Biol 2006; 26(19):7155–7166.PubMedCrossRefGoogle Scholar
  65. 65.
    Houtman JC, Yamaguchi H, Barda-Saad M et al. Oligomerization of signaling complexes by the multipoint binding of GRB2 to both LAT and SOS1. Nat Struct Mol Biol 2006; 13(9):798–805.PubMedCrossRefGoogle Scholar
  66. 66.
    Anderson RG, Jacobson K. A role for lipid shells in targeting proteins to caveolae, rafts and other lipid domains. Science 2002; 296(5574):1821–1825.PubMedCrossRefGoogle Scholar
  67. 67.
    Rivnay B, Wank SA, Poy G et al. Phospholipids stabilize the interaction between the alpha-subunit and beta-subunit of the solubilized receptor for immunoglobulin-E. Biochemistry 1982; 21(26):6922–6927.PubMedCrossRefGoogle Scholar
  68. 68.
    Rivnay B, Fischer G. Phospholipid distribution in the microenvironment of the immunoglobulin E-receptor from rat basophilic leukemia-cell membrane. Biochemistry 1986; 25(19):5686–5693.PubMedCrossRefGoogle Scholar
  69. 69.
    Kinet JP, Quarto R, Perezmontfort R et al. Noncovalently and covalently bound lipid on the receptor for immunoglobulin-E. Biochemistry 1985; 24(25):7342–7348.PubMedCrossRefGoogle Scholar
  70. 70.
    Sheets ED, Holowka D, Baird B. Critical role for cholesterol in Lyn-mediated tyrosine phosphorylation of Fc epsilon RI and their association with detergent-resistant membranes. J Cell Biol 1999; 145(4):877–887.PubMedCrossRefGoogle Scholar
  71. 71.
    Surviladze Z, Harrison KA, Murphy RC et al. Fc epsilon RI and Thy-1 domains have unique protein and lipid compositions. J Lipid Res 2007; 48(6): 1325–1335.PubMedCrossRefGoogle Scholar
  72. 72.
    Yamashita T, Yamaguchi T, Murakami K et al. Detergent-resistant membrane domains are required for mast cell activation but dispensable for tyrosine phosphorylation upon aggregation of the high affinity receptor for IgE. J Biochem 2001; 129(6):861–868.PubMedGoogle Scholar
  73. 73.
    Wilson BS, Steinberg SL, Liederman K et al. Markers for detergent-resistant lipid rafts occupy distinct and dynamic domains in native membranes. Mol Biol Cell 2004; 15(6):2580–2592.PubMedCrossRefGoogle Scholar
  74. 74.
    Surviladze Z, Harrison KA, Murphy RC et al. FcepsilonRI and Thy-1 domains have unique protein and lipid compositions. J Lipid Res 2007; 48(6): 1325–1335.PubMedCrossRefGoogle Scholar
  75. 75.
    Pike LJ, Han X, Gross RW. Epidermal growth factor receptors are localized to lipid rafts that contain a balance of inner and outer leaflet lipids: a shotgun lipidomics study. J Biol Chem 2005; 280(29):26796–26804.PubMedCrossRefGoogle Scholar
  76. 76.
    Gorgas K, Teigler A, Komljenovic D et al. The ether lipid-deficient mouse: tracking down plasmalogen functions. Biochim Biophys Acta 2006; 1763(12):1511–1526.PubMedCrossRefGoogle Scholar
  77. 77.
    Kovarova M, Wassif CA, Odom S et al. Cholesterol deficiency in a mouse model of smith-lemli-opitz syndrome reveals increased mast cell responsiveness. J Exp Med 2006; 203(5): 1161–1171.PubMedCrossRefGoogle Scholar
  78. 78.
    Dustin ML. A dynamic view of the immunological synapse. Semin Immunol 2005; 17(6):400–410.PubMedCrossRefGoogle Scholar
  79. 79.
    Tolar P, Hanna J, Krueger PD et al. The constant region of the membrane immunoglobulin mediates B-Cell-Receptor clustering and signaling in response to membrane antigens. Immunity 2009; 30(1):44–55.PubMedCrossRefGoogle Scholar
  80. 80.
    Sprong H, van der Sluijs P, van Meer G. How proteins move lipids and lipids move proteins. Nat Rev Mol Cell Biol 2001; 2(7):504–513.PubMedCrossRefGoogle Scholar
  81. 81.
    Thiele C, Hannah MJ, Fahrenholz F et al. Cholesterol binds to synaptophysin and is required for biogenesis of synaptic vesicles. Nat Cell Biol 2000; 2(1):42–49.PubMedCrossRefGoogle Scholar
  82. 82.
    Epand RM. Cholesterol and the interaction of proteins with membrane domains. Prog Lipid Res 2006; 45(4):279–294.PubMedCrossRefGoogle Scholar
  83. 83.
    Huttner WB, Zimmerberg J. Implications of lipid microdomains for membrane curvature, budding and fission—commentary. Curr Opin Cell Biol 2001; 13(4):478–484.PubMedCrossRefGoogle Scholar
  84. 84.
    Paar JM, Harris NT, Holowka D et al. Bivalent ligands with rigid double-stranded DNA spacers reveal structural constraints on signaling by Fc epsilon RI. J Immunol 2002; 169(2):856–864.PubMedGoogle Scholar
  85. 85.
    Stauffer TP, Meyer T. Compartmentalized IgE receptor-mediated signal transduction in living cells. J Cell Biol 1997; 139(6): 1447–1454.PubMedCrossRefGoogle Scholar
  86. 86.
    Larson DR, Gosse JA, Holowka DA et al. Temporally resolved interactions between IgE receptors and Lyn kinase on living cells measured by 2-photon fluorescence correlation spectroscopy. Microsc Microanal 2007; 13:8–9.CrossRefGoogle Scholar
  87. 87.
    Lidke DS, Wilson BS. Caught in the act: quantifying protein behaviour in living cells. Trends Cell Biol 2009; 19(11):566–574.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2011

Authors and Affiliations

  • Bridget S. Wilson
    • 1
  • Janet M. Oliver
    • 1
  • Diane S. Lidke
    • 1
  1. 1.Department of PathologyUniversity of New Mexico AlbuquerqueNew MexicoUSA

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