Seminars in Immunopathology

, Volume 40, Issue 6, pp 605–615 | Cite as

Picket-fences in the plasma membrane: functions in immune cells and phagocytosis

  • Sivakami M. Mylvaganam
  • Sergio Grinstein
  • Spencer A. FreemanEmail author


Recent studies of molecular mobility in the plasma membrane have revealed that diffusion is restricted by cytoskeletal networks or fences. Transmembrane protein “pickets” that reversibly associate with the membrane-associated skeleton and with the pericellular coat impede the movement of unattached bystander molecules. While membrane picket-fences were originally described as barriers to free diffusion in more passive cell types such as fibroblasts, they have particularly important functions in the more dynamic immune cells. In phagocytes, such fences curtail spontaneous activation and their disassembly facilitates stimulation by target particles, fostering receptor clustering and the exclusion of phosphatases from the phagocytic cup. In this review, we describe the nature of the cellular cytoskeleton and of the exoskeleton created by the pericellular coat, their association with transmembrane pickets, and the modulation of molecular mobility during phagocytosis.


Macrophage Cytoskeleton F-actin Spectrin Glycocalyx Single-particle tracking Diffusion CD44 CD45 


Funding information

S.A.F. is supported by a Banting fellowship of the Canadian Institutes of Health Research (CIHR). S.G. is supported by grant FDN-143202 from CIHR.


  1. 1.
    Flannagan RS, Jaumouille V, Grinstein S (2012) The cell biology of phagocytosis. Annu Rev Pathol 7:61–98PubMedCrossRefGoogle Scholar
  2. 2.
    Ravichandran KS, Lorenz U (2007) Engulfment of apoptotic cells: signals for a good meal. Nat Rev Immunol 7(12):964–974PubMedCrossRefGoogle Scholar
  3. 3.
    Schrijvers DM, De Meyer GR, Herman AG, Martinet W (2007) Phagocytosis in atherosclerosis: molecular mechanisms and implications for plaque progression and stability. Cardiovasc Res 73(3):470–480PubMedCrossRefGoogle Scholar
  4. 4.
    Gordon SR, Maute RL, Dulken BW, Hutter G, George BM, McCracken MN, Gupta R, Tsai JM, Sinha R, Corey D, Ring AM, Connolly AJ, Weissman IL (2017) PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity. Nature 545(7655):495–499PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Freeman SA, Grinstein S (2014) Phagocytosis: receptors, signal integration, and the cytoskeleton. Immunol Rev 262(1):193–215PubMedCrossRefGoogle Scholar
  6. 6.
    Jones DH, Nusbacher J, Anderson CL (1985) Fc receptor-mediated binding and endocytosis by human mononuclear phagocytes: monomeric IgG is not endocytosed by U937 cells and monocytes. J Cell Biol 100:558–564PubMedCrossRefGoogle Scholar
  7. 7.
    Turrini F, Arese P, Yuan J, Low PS (1991) Clustering of integral membrane proteins of the human erythrocyte membrane stimulates autologous IgG binding, complement deposition, and phagocytosis. J Biol Chem 266(35):23611–23617PubMedGoogle Scholar
  8. 8.
    Cox D, Greenberg S (2001) Phagocytic signaling strategies: Fc(gamma)receptor-mediated phagocytosis as a model system. Semin Immunol 13(6):339–345PubMedCrossRefGoogle Scholar
  9. 9.
    Swanson JA, Hoppe AD (2004) The coordination of signaling during Fc receptor-mediated phagocytosis. J Leukoc Biol 76(6):1093–1103PubMedCrossRefGoogle Scholar
  10. 10.
    Goodridge HS, Reyes CN, Becker CA, Katsumoto TR, Ma J, Wolf AJ, Bose N, Chan ASH, Magee AS, Danielson ME, Weiss A, Vasilakos JP, Underhill DM (2011) Activation of the innate immune receptor Dectin-1 upon formation of a ‘phagocytic synapse’. Nature 472(7344):471–475PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Freeman SA, Goyette J, Furuya W, Woods EC, Bertozzi CR, Bergmeier W, Hinz B, van der Merwe PA, Das R, Grinstein S (2016) Integrins form an expanding diffusional barrier that coordinates phagocytosis. Cell 164(1–2):128–140PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Bakalar MH, Joffe AM, Schmid EM, Son S, Podolski M, Fletcher DA (2018) Size-dependent segregation controls macrophage phagocytosis of antibody-opsonized targets. Cell 174(1):131–142 e113PubMedCrossRefGoogle Scholar
  13. 13.
    Chang VT, Fernandes RA, Ganzinger KA, Lee SF, Siebold C, McColl J, Jönsson P, Palayret M, Harlos K, Coles CH, Jones EY, Lui Y, Huang E, Gilbert RJC, Klenerman D, Aricescu AR, Davis SJ (2016) Initiation of T cell signaling by CD45 segregation at ‘close contacts’. Nat Immunol 17(5):574–582PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Jongstra-Bilen J, Harrison R, Grinstein S (2003) Fcgamma-receptors induce Mac-1 (CD11b/CD18) mobilization and accumulation in the phagocytic cup for optimal phagocytosis. J Biol Chem 278(46):45720–45729PubMedCrossRefGoogle Scholar
  15. 15.
    Luo BH, Carman CV, Springer TA (2007) Structural basis of integrin regulation and signaling. Annu Rev Immunol 25:619–647PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Li X, Utomo A, Cullere X, Choi MM, Milner DA Jr, Venkatesh D, Yun SH, Mayadas TN (2011) The beta-glucan receptor Dectin-1 activates the integrin Mac-1 in neutrophils via Vav protein signaling to promote Candida albicans clearance. Cell Host Microbe 10(6):603–615PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Maxson ME, Naj X, O’Meara TR, Plumb JD, Cowen LE, Grinstein S (2018) Integrin-based diffusion barrier separates membrane domains enabling the formation of microbiostatic frustrated phagosomes. Elife 7:e34798.
  18. 18.
    van Spriel AB, Leusen JH, van Egmond M, Dijkman HB, Assmann KJ, Mayadas TN, van de Winkel J (2001) Mac-1 (CD11b/CD18) is essential for Fc receptor-mediated neutrophil cytotoxicity and immunologic synapse formation. Blood 97(8):2478–2486PubMedCrossRefGoogle Scholar
  19. 19.
    Singer SJ, Nicolson GL (1972) The fluid mosaic model of the structure of cell membranes. Science 175:720–731PubMedCrossRefGoogle Scholar
  20. 20.
    Saxton MJ, Jacobson K (1997) Single-particle tracking: applications to membrane dynamics. Annu Rev Biophys Biomol Struct 26:373–399PubMedCrossRefGoogle Scholar
  21. 21.
    Jacobson K, Sheets ED, Simson R (1995) Revisiting the fluid mosaic model of membranes. Science 268(5216):1441–1442PubMedCrossRefGoogle Scholar
  22. 22.
    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
  23. 23.
    Kusumi A, Fujiwara TK, Chadda R, Xie M, Tsunoyama TA, Kalay Z, Kasai RS, Suzuki KGN (2012) Dynamic organizing principles of the plasma membrane that regulate signal transduction: commemorating the fortieth anniversary of Singer and Nicolson’s fluid-mosaic model. Annu Rev Cell Dev Biol 28:215–250PubMedCrossRefGoogle Scholar
  24. 24.
    Fujiwara T, Ritchie K, Murakoshi H, Jacobson K, Kusumi A (2002) Phospholipids undergo hop diffusion in compartmentalized cell membrane. J Cell Biol 157(6):1071–1081PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Suzuki K, Ritchie K, Kajikawa E, Fujiwara T, Kusumi A (2005) Rapid hop diffusion of a G-protein-coupled receptor in the plasma membrane as revealed by single-molecule techniques. Biophys J 88(5):3659–3680PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Morone N, Fujiwara T, Murase K, Kasai RS, Ike H, Yuasa S, Usukura J, Kusumi A (2006) Three-dimensional reconstruction of the membrane skeleton at the plasma membrane interface by electron tomography. J Cell Biol 174(6):851–862PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Freeman SA, Vega A, Riedl M, Collins RF, Ostrowski PP, Woods EC, Bertozzi CR, Tammi MI, Lidke DS, Johnson P, Mayor S, Jaqaman K, Grinstein S (2018) Transmembrane pickets connect cyto- and pericellular skeletons forming barriers to receptor engagement. Cell 172(1–2):305–317 e310PubMedCrossRefGoogle Scholar
  28. 28.
    Sheets ED, Lee GM, Simson R, Jacobson K (1997) Transient confinement of a glycosylphosphatidylinositol-anchored protein in the plasma membrane. Biochemistry 36(41):12449–12458PubMedCrossRefGoogle Scholar
  29. 29.
    Saha S, Lee IH, Polley A, Groves JT, Rao M, Mayor S (2015) Diffusion of GPI-anchored proteins is influenced by the activity of dynamic cortical actin. Mol Biol Cell 26(22):4033–4045PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Fischer H, Polikarpov I, Craievich AF (2004) Average protein density is a molecular-weight-dependent function. Protein Sci 13(10):2825–2828PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Frick M, Schmidt K, Nichols BJ (2007) Modulation of lateral diffusion in the plasma membrane by protein density. Curr Biol 17(5):462–467PubMedCrossRefGoogle Scholar
  32. 32.
    Israelachvili J, Wennerstrom H (1996) Role of hydration and water structure in biological and colloidal interactions. Nature 379:219–225PubMedCrossRefGoogle Scholar
  33. 33.
    Allen TW, Anderson OS, Roux B (2004) On the importance of atomic fluctuations, protein flexibility, and solvent in ion permeation. J Gen Physiol 124(6):679–690PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Cunha SR, Mohler PJ (2009) Ankyrin protein networks in membrane formation and stabilization. J Cell Mol Med 13(11–12):4364–4376PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Lu PW, Soong CJ, Tao M (1985) Phosphorylation of ankyrin decreases its affinity for spectrin tetramer. J Biol Chem 260(28):14958–14964PubMedGoogle Scholar
  36. 36.
    Bennett V, Baines AJ (2001) Spectrin and ankyrin-based pathways: metazoan inventions for integrating cells into tissues. Physiol Rev 81(3):1353–1392PubMedCrossRefGoogle Scholar
  37. 37.
    Cianci CD, Giorgi M, Morrow JS (1988) Phosphorylation of ankyrin down-regulates its cooperative interaction with spectrin and protein 3. J Cell Biochem 37(3):301–315PubMedCrossRefGoogle Scholar
  38. 38.
    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(1):37–51PubMedCrossRefGoogle Scholar
  39. 39.
    Fehon RG, McClatchey AI, Bretscher A (2010) Organizing the cell cortex: the role of ERM proteins. Nat Rev Mol Cell Biol. 11:276–287PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Ostrowski PP, Grinstein S, Freeman SA (2016) Diffusion barriers, mechanical forces, and the biophysics of phagocytosis. Dev Cell 38(2):135–146PubMedCrossRefGoogle Scholar
  41. 41.
    Moser M, Legate KR, Zent R, Fassler R (2009) The tail of integrins, talin, and kindlins. Science 324(5929):895–899PubMedCrossRefGoogle Scholar
  42. 42.
    Sheetz MP, Schindler M, Koppel DE (1980) Lateral mobility of integral membrane proteins is increased spherocytic erythrocytes. Nature 285:510–512PubMedCrossRefGoogle Scholar
  43. 43.
    Tsuji A, Ohnishi S (1986) Restriction of the lateral motion of band-3 in the erythrocyte-membrane by the cytoskeletal network: dependence on spectrin association state. Biochemistry 25:6133–6139PubMedCrossRefGoogle Scholar
  44. 44.
    Tsuji A, Kawasaki K, Ohnishi S, Merkle H, Kusumi A (1988) Regulation of band-3 mobilities in erythrocyte ghost membranes by protein association and cytoskeletal meshwork. Biochemistry 27:7447–7452PubMedCrossRefGoogle Scholar
  45. 45.
    Xu K, Zhong G, Zhuang X (2013) Actin, spectrin, and associated proteins form a periodic cytoskeletal structure in axons. Science 339(6118):452–456PubMedCrossRefGoogle Scholar
  46. 46.
    Nakada C, Ritchie K, Oba Y, Nakamura M, Hotta Y, Iino R, Kasai RS, Yamaguchi K, Fujiwara T, Kusumi A (2003) Accumulation of anchored proteins forms membrane diffusion barriers during neuronal polarization. Nat Cell Biol 5(7):626–632PubMedCrossRefGoogle Scholar
  47. 47.
    Kobayashi T, Storrie B, Simons K, Dotti CG (1992) A functional barrier to movement of lipids in polarized neurons. Nature 359:647–650PubMedCrossRefGoogle Scholar
  48. 48.
    Winckler B, Forscher P, Mellman I (1999) A diffusion barrier maintains distribution of membrane proteins in polarized neurons. Nature 397:698–701PubMedCrossRefGoogle Scholar
  49. 49.
    Winckler B, Mellman I (1999) Neuronal polarity: controlling the sorting and diffusion of membrane components. Neuron 23:637–640PubMedCrossRefGoogle Scholar
  50. 50.
    Albrecht D, Winterflood CM, Sadeghi M, Tschager T, Noe F, Ewers H (2016) Nanoscopic compartmentalization of membrane protein motion at the axon initial segment. J Cell Biol 215(1):37–46PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Monroe JG (2004) Ligand-independent tonic signaling in B-cell receptor function. Curr Opin Immunol 16(3):288–295PubMedCrossRefGoogle Scholar
  52. 52.
    Treanor B, Depoil D, Gonzalez-Granja A, Barral P, Weber M, Dushek O, Bruckbauer A, Batista FD (2010) The membrane skeleton controls diffusion dynamics and signaling through the B cell receptor. Immunity 32(2):187–199PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Andrews NL, Lidke KA, Pfeiffer JR, Burns AR, Wilson BS, Oliver JM, Lidke DS (2008) Actin restricts FcepsilonRI diffusion and facilitates antigen-induced receptor immobilization. Nat Cell Biol 10(8):955–963PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Eisenmann KM, Harris ES, Kitchen SM, Holman HA, Higgs HN, Alberts AS (2007) Dia-interacting protein modulates formin-mediated actin assembly at the cell cortex. Curr Biol 17(7):579–591PubMedCrossRefGoogle Scholar
  55. 55.
    Chesarone MA, DuPage AG, Goode BL (2010) Unleashing formins to remodel the actin and microtubule cytoskeletons. Nat Rev Mol Cell Biol 11(1):62–74PubMedCrossRefGoogle Scholar
  56. 56.
    Jaumouillé V, Farkash Y, Jaqaman K, Das R, Lowell CA, Grinstein S (2014) Actin cytoskeleton reorganization by Syk regulates Fcγ receptor responsiveness by increasing its lateral mobility and clustering. Dev Cell 29(5):534–546. PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Kage F, Winterhoff M, Dimchev V, Mueller J, Thalheim T, Freise A, Brühmann S, Kollasser J, Block J, Dimchev G, Geyer M, Schnittler HJ, Brakebusch C, Stradal TEB, Carlier MF, Sixt M, Käs J, Faix J, Rottner K (2017) FMNL formins boost lamellipodial force generation. Nat Commun 8:14832PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Jaiswal R, Breitsprecher D, Collins A, Correa IR Jr, Xu MQ, Goode BL (2013) The formin Daam1 and fascin directly collaborate to promote filopodia formation. Curr Biol 23(14):1373–1379PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Ramalingam N, Franke C, Jaschinski E, Winterhoff M, Lu Y, Brühmann S, Junemann A, Meier H, Noegel AA, Weber I, Zhao H, Merkel R, Schleicher M, Faix J (2015) A resilient formin-derived cortical actin meshwork in the rear drives actomyosin-based motility in 2D confinement. Nat Commun 6:8496PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Goley ED, Welch MD (2006) The ARP2/3 complex: an actin nucleator comes of age. Nat Rev Mol Cell Biol 7(10):713–726PubMedCrossRefGoogle Scholar
  61. 61.
    Campellone KG, Welch MD (2010) A nucleator arms race: cellular control of actin assembly. Nat Rev Mol Cell Biol 11(4):237–251PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Bovellan M, Romeo Y, Biro M, Boden A, Chugh P, Yonis A, Vaghela M, Fritzsche M, Moulding D, Thorogate R, Jégou A, Thrasher AJ, Romet-Lemonne G, Roux PP, Paluch EK, Charras G (2014) Cellular control of cortical actin nucleation. Curr Biol 24(14):1628–1635PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Stossel TP (1993) On the crawling of animal cells. Science 260(5111):1086–1094PubMedCrossRefGoogle Scholar
  64. 64.
    Burke TA, Christensen JR, Barone E, Suarez C, Sirotkin V, Kovar DR (2014) Homeostatic actin cytoskeleton networks are regulated by assembly factor competition for monomers. Curr Biol 24(5):579–585PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Sanz-Moreno V, Gadea G, Ahn J, Paterson H, Marra P, Pinner S, Sahai E, Marshall CJ (2008) Rac activation and inactivation control plasticity of tumor cell movement. Cell 135(3):510–523PubMedCrossRefGoogle Scholar
  66. 66.
    Hayakawa K, Tatsumi H, Sokabe M (2011) Actin filaments function as a tension sensor by tension-dependent binding of cofilin to the filament. J Cell Biol 195(5):721–727PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Schmoller KM, Semmrich C, Bausch AR (2011) Slow down of actin depolymerization by cross-linking molecules. J Struct Biol 173(2):350–357PubMedCrossRefGoogle Scholar
  68. 68.
    Mukhina S, Wang YL, Murata-Hori M (2007) Alpha-actinin is required for tightly regulated remodeling of the actin cortical network during cytokinesis. Dev Cell 13(4):554–565PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Sanders LC, Matsumura F, Bokoch GM, de Lanerolle P (1999) Inhibition of myosin light chain kinase by p21-activated kinase. Science 283(5410):2083–2085PubMedCrossRefGoogle Scholar
  70. 70.
    Lomakin AJ, Lee KC, Han SJ, Bui DA, Davidson M, Mogilner A, Danuser G (2015) Competition for actin between two distinct F-actin networks defines a bistable switch for cell polarization. Nat Cell Biol 17(11):1435–1445PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Watanabe N, Madaule P, Reid T, Ishizaki T, Watanabe G, Kakizuka A, Saito Y, Nakao K, Jockusch BM, Narumiya S (1997) p140mDia, a mammalian homolog of Drosophila diaphanous, is a target protein for Rho small GTPase and is a ligand for profilin. EMBO J 16(11):3044–3056PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Breitsprecher D, Goode BL (2013) Formins at a glance. J Cell Sci 126(Pt 1):1–7PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Cox D, Chang P, Zhang Q, Reddy PG, Bokoch GM, Greenberg S (1997) Requirements for both Rac1 and Cdc42 in membrane ruffling and phagocytosis in leukocytes. J Exp Med 186(9):1487–1494PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Ridley AJ, Paterson HF, Johnston CL, Diekmann D, Hall A (1992) The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell 70(3):401–410PubMedCrossRefGoogle Scholar
  75. 75.
    Koronakis V, Hume PJ, Humphreys D, Liu T, Horning O, Jensen ON, McGhie EJ (2011) WAVE regulatory complex activation by cooperating GTPases Arf and Rac1. Proc Natl Acad Sci U S A 108(35):14449–14454PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Ohta Y, Hartwig JH, Stossel TP (2006) FilGAP, a Rho- and ROCK-regulated GAP for Rac binds filamin A to control actin remodelling. Nat Cell Biol 8(8):803–814PubMedCrossRefGoogle Scholar
  77. 77.
    Sander EE, ten Klooster JP, van Delft S, van der Kammen RA, Collard JG (1999) Rac downregulates Rho activity: reciprocal balance between both GTPases determines cellular morphology and migratory behavior. J Cell Biol 147(5):1009–1022PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Flannagan RS, Harrison RE, Yip CM, Jaqaman K, Grinstein S (2010) Dynamic macrophage “probing” is required for the efficient capture of phagocytic targets. J Cell Biol 191:1205–1218PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Jaumouille V, Farkash Y, Jaqaman K, Das R, Lowell CA, Grinstein S (2014) Actin cytoskeleton reorganization by Syk regulates Fcgamma receptor responsiveness by increasing its lateral mobility and clustering. Dev Cell 29(5):534–546PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Jaqaman K, Kuwata H, Touret N, Collins R, Trimble WS, Danuser G, Grinstein S (2011) Cytoskeletal control of CD36 diffusion promotes its receptor and signaling function. Cell 146(6):593–606PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Bourguignon LY, Lokeshwar VB, He J, Chen X, Bourguignon GJ (1992) A CD44-like endothelial cell transmembrane glycoprotein (GP116) interacts with extracellular matrix and ankyrin. Mol Cell Biol 12(10):4464–4471PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Caron E, Self AJ, Hall A (2000) The GTPase Rap1 controls functional activation of macrophage integrin alphaMbeta2 by LPS and other inflammatory mediators. Curr Biol 10:974–978PubMedCrossRefGoogle Scholar
  83. 83.
    Williams LM, Ridley AJ (2000) Lipopolysaccharide induces actin reorganization and tyrosine phosphorylation of Pyk2 and paxillin in monocytes and macrophages. J Immunol 164:2028–2036PubMedCrossRefGoogle Scholar
  84. 84.
    Underhill DM, Goodridge HS (2012) Information processing during phagocytosis. Nat Rev Immunol 12(7):492–502PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    West MA, Wallin RP, Matthews SP, Svensson HG, Zaru R, Ljunggren HG, Prescott AR, Watts C (2004) Enhanced dendritic cell antigen capture via toll-like receptor-induced actin remodeling. Science 305(5687):1153–1157PubMedCrossRefGoogle Scholar
  86. 86.
    Weiss-Haljiti C, Pasquali C, Ji H, Gillieron C, Chabert C, Curchod ML, Hirsch E, Ridley AJ, van Huijsduijnen RH, Camps M, Rommel C (2004) Involvement of phosphoinositide 3-kinase gamma, Rac, and PAK signaling in chemokine-induced macrophage migration. J Biol Chem 279(41):43273–43284PubMedCrossRefGoogle Scholar
  87. 87.
    Matsui S, Matsumoto S, Adachi R, Kusui K, Hirayama A, Watanabe H, Ohashi K, Mizuno K, Yamaguchi T, Kasahara T, Suzuki K (2002) LIM kinase 1 modulates opsonized zymosan-triggered activation of macrophage-like U937 cells. Possible involvement of phosphorylation of cofilin and reorganization of actin cytoskeleton. J Biol Chem 277(1):544–549PubMedCrossRefGoogle Scholar
  88. 88.
    Vargas P, Maiuri P, Bretou M et al (2016) Innate control of actin nucleation determines two distinct migration behaviours in dendritic cells. Nat Cell Biol 135:510–523Google Scholar
  89. 89.
    Ghosh M, Song X, Mouneimne G, Sidani M, Lawrence DS, Condeelis JS (2004) Cofilin promotes actin polymerization and defines the direction of cell motility. Science 304(5671):743–746PubMedCrossRefGoogle Scholar
  90. 90.
    Martin WL, West AP Jr, Gan L, Bjorkman PJ (2001) Crystal structure at 2.8 A of an FcRn/heterodimeric Fc complex: mechanism of pH-dependent binding. Mol Cell 7(4):867–877PubMedCrossRefGoogle Scholar
  91. 91.
    Brown J, O’Callaghan CA, Marshall AS et al (2007) Structure of the fungal beta-glucan-binding immune receptor dectin-1: implications for function. Protein Sci 16(6):1042–1052PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Wykes M, MacDonald KP, Tran M, Quin RJ, Xing PX, Gendler SJ, Hart DN, McGuckin M (2002) MUC1 epithelial mucin (CD227) is expressed by activated dendritic cells. J Leukoc Biol 72(4):692–701PubMedGoogle Scholar
  93. 93.
    Xu X, Padilla MT, Li B, Wells A, Kato K, Tellez C, Belinsky SA, Kim KC, Lin Y (2014) MUC1 in macrophage: contributions to cigarette smoke-induced lung cancer. Cancer Res 74(2):460–470PubMedCrossRefGoogle Scholar
  94. 94.
    Wesseling J, van der Valk SW, Vos HL (1995) Episialin (MUC1) overexpression inhibits integrin-mediated cell adhesion to extracellular matrix components. J Cell Biol 129:255–265PubMedCrossRefGoogle Scholar
  95. 95.
    Lesley J, Hascall VC, Tammi M, Hyman R (2000) Hyaluronan binding by cell surface CD44. J Biol Chem 275(35):26967–26975PubMedGoogle Scholar
  96. 96.
    Lajoie P, Goetz JG, Dennis JW, Nabi IR (2009) Lattices, rafts, and scaffolds: domain regulation of receptor signaling at the plasma membrane. J Cell Biol 185:381–385PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Erasmus MF, Matlawska-Wasowska K, Kinjyo I, Mahajan A, Winter SS, Xu L, Horowitz M, Lidke DS, Wilson BS (2016) Dynamic pre-BCR homodimers fine-tune autonomous survival signals in B cell precursor acute lymphoblastic leukemia. Sci Signal 9(456):ra116PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Liu SD, Tomassian T, Bruhn KW, Miller JF, Poirier F, Miceli MC (2009) Galectin-1 tunes TCR binding and signal transduction to regulate CD8 burst size. J Immunol 182(9):5283–5295PubMedCrossRefGoogle Scholar
  99. 99.
    Lutomski D, Fouillit M, Bourin P, Mellottée D, Denize N, Pontet M, Bladier D, Caron M, Joubert-Caron R (1997) Externalization and binding of galectin-1 on cell surface of K562 cells upon erythroid differentiation. Glycobiology 7(8):1193–1199PubMedCrossRefGoogle Scholar
  100. 100.
    Cao A, Alluqmani N, Buhari FHM, Wasim L, Smith LK, Quaile AT, Shannon M, Hakim Z, Furmli H, Owen DM, Savchenko A, Treanor B (2018) Galectin-9 binds IgM-BCR to regulate B cell signaling. Nat Commun 9(1):3288PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Ghazizadeh S, Bolen JB, Fleit HB (1994) Physical and functional association of Src-related protein tyrosine kinases with FcgRII in monocytic THP-1 cells. J Biol Chem 269:8878–8884PubMedGoogle Scholar
  102. 102.
    Davis SJ, van der Merwe PA (2006) The kinetic-segregation model: TCR triggering and beyond. Nat Immunol 7(8):803–809PubMedCrossRefGoogle Scholar
  103. 103.
    Chen J, Zhong MC, Guo H, Davidson D, Mishel S, Lu Y, Rhee I, Pérez-Quintero LA, Zhang S, Cruz-Munoz ME, Wu N, Vinh DC, Sinha M, Calderon V, Lowell CA, Danska JS, Veillette A (2017) SLAMF7 is critical for phagocytosis of haematopoietic tumour cells via Mac-1 integrin. Nature 544(7651):493–497PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Hsu TY, Wu YC (2010) Engulfment of apoptotic cells in C. elegans is mediated by integrin alpha/SRC signaling. Current biology : CB 20(6):477–486PubMedCrossRefGoogle Scholar
  105. 105.
    Wu Y, Singh S, Georgescu MM, Birge RB (2005) A role for Mer tyrosine kinase in alphavbeta5 integrin-mediated phagocytosis of apoptotic cells. J Cell Sci 118(Pt 3):539–553PubMedCrossRefGoogle Scholar
  106. 106.
    Arandjelovic S, Ravichandran KS (2015) Phagocytosis of apoptotic cells in homeostasis. Nat Immunol 16(9):907–917PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Rowley RB, Burkhardt AL, Chao HG, Matsueda GR, Bolen JB (1995) Syk protein-tyrosine kinase is regulated by tyrosine-phosphorylated Ig alpha/Ig beta immunoreceptor tyrosine activation motif binding and autophosphorylation. J Biol Chem 270(19):11590–11594PubMedCrossRefGoogle Scholar
  108. 108.
    Marshall JG, Booth JW, Stambolic V, Mak T, Balla T, Schreiber AD, Meyer T, Grinstein S (2001) Restricted accumulation of phosphatidylinositol 3-kinase products in a plasmalemmal subdomain during Fc gamma receptor-mediated phagocytosis. J Cell Biol 153(7):1369–1380PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Law CL, Chandran KA, Sidorenko SP, Clark EA (1996) Phospholipase C-gamma1 interacts with conserved phosphotyrosyl residues in the linker region of Syk and is a substrate for Syk. Mol Cell Biol 16(4):1305–1315PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Hao JJ, Liu Y, Kruhlak M, Debell KE, Rellahan BL, Shaw S (2009) Phospholipase C-mediated hydrolysis of PIP2 releases ERM proteins from lymphocyte membrane. J Cell Biol 184(3):451–462PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Zhang Y, Du G (2009) Phosphatidic acid signaling regulation of Ras superfamily of small guanosine triphosphatases. Biochim Biophys Acta 1791(9):850–855PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Nag S, Larsson M, Robinson RC, Burtnick LD (2013) Gelsolin: the tail of a molecular gymnast. Cytoskeleton (Hoboken) 70(7):360–384CrossRefGoogle Scholar
  113. 113.
    Bierne H, Gouin E, Roux P, Caroni P, Yin HL, Cossart P (2001) A role for cofilin and LIM kinase in Listeria-induced phagocytosis. J Cell Biol 155(1):101–112PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Mizuno K (2013) Signaling mechanisms and functional roles of cofilin phosphorylation and dephosphorylation. Cell Signal 25(2):457–469PubMedCrossRefGoogle Scholar
  115. 115.
    Hoppe AD, Swanson JA (2004) Cdc42, Rac1, and Rac2 display distinct patterns of activation during phagocytosis. Mol Biol Cell 15(8):3509–3519PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Banjade S, Rosen MK (2014) Phase transitions of multivalent proteins can promote clustering of membrane receptors. Elife 3.
  117. 117.
    Dart AE, Donnelly SK, Holden DW, Way M, Caron E (2012) Nck and Cdc42 co-operate to recruit N-WASP to promote FcgammaR-mediated phagocytosis. J Cell Sci 125(Pt 12):2825–2830PubMedCrossRefGoogle Scholar
  118. 118.
    Blasutig IM, New LA, Thanabalasuriar A, Dayarathna TK, Goudreault M, Quaggin SE, Li SSC, Gruenheid S, Jones N, Pawson T (2008) Phosphorylated YDXV motifs and Nck SH2/SH3 adaptors act cooperatively to induce actin reorganization. Mol Cell Biol 28(6):2035–2046PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    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(Pt 23):4307–4318PubMedGoogle Scholar
  120. 120.
    Rohatgi R, Ho HY, Kirschner MW (2000) Mechanism of N-WASP activation by CDC42 and phosphatidylinositol 4, 5-bisphosphate. J Cell Biol 150(6):1299–1310PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Pearson AM, Baksa K, Ramet M et al (2003) Identification of cytoskeletal regulatory proteins required for efficient phagocytosis in Drosophila. Microbes Infect 5(10):815–824PubMedCrossRefGoogle Scholar
  122. 122.
    Grimsley CM, Kinchen JM, Tosello-Trampont AC, Brugnera E, Haney LB, Lu M, Chen Q, Klingele D, Hengartner MO, Ravichandran KS (2004) Dock180 and ELMO1 proteins cooperate to promote evolutionarily conserved Rac-dependent cell migration. J Biol Chem 279(7):6087–6097PubMedCrossRefGoogle Scholar
  123. 123.
    Patel JC, Hall A, Caron E (2002) Vav regulates activation of Rac but not Cdc42 during FcgammaR-mediated phagocytosis. Mol Biol Cell 13(4):1215–1226PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Hall AB, Gakidis MA, Glogauer M et al (2006) Requirements for Vav guanine nucleotide exchange factors and Rho GTPases in FcgammaR- and complement-mediated phagocytosis. Immunity 24(3):305–316PubMedCrossRefGoogle Scholar
  125. 125.
    Koh AL, Sun CX, Zhu F, Glogauer M (2005) The role of Rac1 and Rac2 in bacterial killing. Cell Immunol 235(2):92–97PubMedCrossRefGoogle Scholar
  126. 126.
    Rotty JD, Brighton HE, Craig SL et al (2017) Arp2/3 complex is required for macrophage integrin functions but is dispensable for FcR phagocytosis and in vivo motility. Dev Cell 42(5):498–513 e496PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Schlam D, Bagshaw RD, Freeman SA, Collins RF, Pawson T, Fairn GD, Grinstein S (2015) Phosphoinositide 3-kinase enables phagocytosis of large particles by terminating actin assembly through Rac/Cdc42 GTPase-activating proteins. Nat Commun 6:8623PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Bajno L, Peng XR, Schreiber AD, Moore HP, Trimble WS, Grinstein S (2000) Focal exocytosis of VAMP3-containing vesicles at sites of phagosome formation. J Cell Biol 149(3):697–706PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Program in Cell Biology, Peter Gilgan Centre for Research and LearningHospital for Sick ChildrenTorontoCanada
  2. 2.Department of BiochemistryUniversity of TorontoTorontoCanada
  3. 3.Keenan Research Centre of the Li Ka Shing Knowledge InstituteSt. Michael’s HospitalTorontoCanada

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