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

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Abstract

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.

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References

  1. Flannagan RS, Jaumouille V, Grinstein S (2012) The cell biology of phagocytosis. Annu Rev Pathol 7:61–98

    Article  CAS  PubMed  Google Scholar 

  2. Ravichandran KS, Lorenz U (2007) Engulfment of apoptotic cells: signals for a good meal. Nat Rev Immunol 7(12):964–974

    Article  CAS  PubMed  Google Scholar 

  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):470–480

    Article  CAS  PubMed  Google Scholar 

  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):495–499

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Freeman SA, Grinstein S (2014) Phagocytosis: receptors, signal integration, and the cytoskeleton. Immunol Rev 262(1):193–215

    Article  CAS  PubMed  Google Scholar 

  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 100:558–564

    Article  CAS  PubMed  Google Scholar 

  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):23611–23617

    CAS  PubMed  Google Scholar 

  8. Cox D, Greenberg S (2001) Phagocytic signaling strategies: Fc(gamma)receptor-mediated phagocytosis as a model system. Semin Immunol 13(6):339–345

    Article  CAS  PubMed  Google Scholar 

  9. Swanson JA, Hoppe AD (2004) The coordination of signaling during Fc receptor-mediated phagocytosis. J Leukoc Biol 76(6):1093–1103

    Article  CAS  PubMed  Google Scholar 

  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):471–475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):128–140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 e113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):574–582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):45720–45729

    Article  CAS  PubMed  Google Scholar 

  15. Luo BH, Carman CV, Springer TA (2007) Structural basis of integrin regulation and signaling. Annu Rev Immunol 25:619–647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):603–615

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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. https://doi.org/10.7554/eLife.34798

  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):2478–2486

    Article  PubMed  Google Scholar 

  19. Singer SJ, Nicolson GL (1972) The fluid mosaic model of the structure of cell membranes. Science 175:720–731

    Article  CAS  PubMed  Google Scholar 

  20. Saxton MJ, Jacobson K (1997) Single-particle tracking: applications to membrane dynamics. Annu Rev Biophys Biomol Struct 26:373–399

    Article  CAS  PubMed  Google Scholar 

  21. Jacobson K, Sheets ED, Simson R (1995) Revisiting the fluid mosaic model of membranes. Science 268(5216):1441–1442

    Article  CAS  PubMed  Google Scholar 

  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 34:351–378

    Article  CAS  PubMed  Google Scholar 

  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 28:215–250

    Article  CAS  PubMed  Google Scholar 

  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):1071–1081

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):3659–3680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):851–862

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 e310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Sheets ED, Lee GM, Simson R, Jacobson K (1997) Transient confinement of a glycosylphosphatidylinositol-anchored protein in the plasma membrane. Biochemistry 36(41):12449–12458

    Article  CAS  PubMed  Google Scholar 

  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):4033–4045

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Fischer H, Polikarpov I, Craievich AF (2004) Average protein density is a molecular-weight-dependent function. Protein Sci 13(10):2825–2828

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Frick M, Schmidt K, Nichols BJ (2007) Modulation of lateral diffusion in the plasma membrane by protein density. Curr Biol 17(5):462–467

    Article  CAS  PubMed  Google Scholar 

  32. Israelachvili J, Wennerstrom H (1996) Role of hydration and water structure in biological and colloidal interactions. Nature 379:219–225

    Article  CAS  PubMed  Google Scholar 

  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):679–690

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Cunha SR, Mohler PJ (2009) Ankyrin protein networks in membrane formation and stabilization. J Cell Mol Med 13(11–12):4364–4376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Lu PW, Soong CJ, Tao M (1985) Phosphorylation of ankyrin decreases its affinity for spectrin tetramer. J Biol Chem 260(28):14958–14964

    CAS  PubMed  Google Scholar 

  36. Bennett V, Baines AJ (2001) Spectrin and ankyrin-based pathways: metazoan inventions for integrating cells into tissues. Physiol Rev 81(3):1353–1392

    Article  CAS  PubMed  Google Scholar 

  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):301–315

    Article  CAS  PubMed  Google Scholar 

  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):37–51

    Article  CAS  PubMed  Google Scholar 

  39. Fehon RG, McClatchey AI, Bretscher A (2010) Organizing the cell cortex: the role of ERM proteins. Nat Rev Mol Cell Biol. 11:276–287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ostrowski PP, Grinstein S, Freeman SA (2016) Diffusion barriers, mechanical forces, and the biophysics of phagocytosis. Dev Cell 38(2):135–146

    Article  CAS  PubMed  Google Scholar 

  41. Moser M, Legate KR, Zent R, Fassler R (2009) The tail of integrins, talin, and kindlins. Science 324(5929):895–899

    Article  CAS  PubMed  Google Scholar 

  42. Sheetz MP, Schindler M, Koppel DE (1980) Lateral mobility of integral membrane proteins is increased spherocytic erythrocytes. Nature 285:510–512

    Article  CAS  PubMed  Google Scholar 

  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 25:6133–6139

    Article  CAS  PubMed  Google Scholar 

  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 27:7447–7452

    Article  CAS  PubMed  Google Scholar 

  45. Xu K, Zhong G, Zhuang X (2013) Actin, spectrin, and associated proteins form a periodic cytoskeletal structure in axons. Science 339(6118):452–456

    Article  CAS  PubMed  Google Scholar 

  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):626–632

    Article  CAS  PubMed  Google Scholar 

  47. Kobayashi T, Storrie B, Simons K, Dotti CG (1992) A functional barrier to movement of lipids in polarized neurons. Nature 359:647–650

    Article  CAS  PubMed  Google Scholar 

  48. Winckler B, Forscher P, Mellman I (1999) A diffusion barrier maintains distribution of membrane proteins in polarized neurons. Nature 397:698–701

    Article  CAS  PubMed  Google Scholar 

  49. Winckler B, Mellman I (1999) Neuronal polarity: controlling the sorting and diffusion of membrane components. Neuron 23:637–640

    Article  CAS  PubMed  Google Scholar 

  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):37–46

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Monroe JG (2004) Ligand-independent tonic signaling in B-cell receptor function. Curr Opin Immunol 16(3):288–295

    Article  CAS  PubMed  Google Scholar 

  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):187–199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):955–963

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):579–591

    Article  CAS  PubMed  Google Scholar 

  55. Chesarone MA, DuPage AG, Goode BL (2010) Unleashing formins to remodel the actin and microtubule cytoskeletons. Nat Rev Mol Cell Biol 11(1):62–74

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1016/j.devcel.2014.04.031

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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 8:14832

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):1373–1379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 6:8496

    Article  CAS  PubMed  Google Scholar 

  60. Goley ED, Welch MD (2006) The ARP2/3 complex: an actin nucleator comes of age. Nat Rev Mol Cell Biol 7(10):713–726

    Article  CAS  PubMed  Google Scholar 

  61. Campellone KG, Welch MD (2010) A nucleator arms race: cellular control of actin assembly. Nat Rev Mol Cell Biol 11(4):237–251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):1628–1635

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Stossel TP (1993) On the crawling of animal cells. Science 260(5111):1086–1094

    Article  CAS  PubMed  Google Scholar 

  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):579–585

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):510–523

    Article  CAS  PubMed  Google Scholar 

  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):721–727

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Schmoller KM, Semmrich C, Bausch AR (2011) Slow down of actin depolymerization by cross-linking molecules. J Struct Biol 173(2):350–357

    Article  CAS  PubMed  Google Scholar 

  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):554–565

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Sanders LC, Matsumura F, Bokoch GM, de Lanerolle P (1999) Inhibition of myosin light chain kinase by p21-activated kinase. Science 283(5410):2083–2085

    Article  CAS  PubMed  Google Scholar 

  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):1435–1445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):3044–3056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Breitsprecher D, Goode BL (2013) Formins at a glance. J Cell Sci 126(Pt 1):1–7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):1487–1494

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):401–410

    Article  CAS  PubMed  Google Scholar 

  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):14449–14454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):803–814

    Article  CAS  PubMed  Google Scholar 

  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):1009–1022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 191:1205–1218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):534–546

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):593–606

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):4464–4471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 10:974–978

    Article  CAS  PubMed  Google Scholar 

  83. Williams LM, Ridley AJ (2000) Lipopolysaccharide induces actin reorganization and tyrosine phosphorylation of Pyk2 and paxillin in monocytes and macrophages. J Immunol 164:2028–2036

    Article  CAS  PubMed  Google Scholar 

  84. Underhill DM, Goodridge HS (2012) Information processing during phagocytosis. Nat Rev Immunol 12(7):492–502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):1153–1157

    Article  CAS  PubMed  Google Scholar 

  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):43273–43284

    Article  CAS  PubMed  Google Scholar 

  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):544–549

    Article  CAS  PubMed  Google Scholar 

  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 135:510–523

    Google Scholar 

  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):743–746

    Article  CAS  PubMed  Google Scholar 

  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):867–877

    Article  CAS  PubMed  Google Scholar 

  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):1042–1052

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):692–701

    CAS  PubMed  Google Scholar 

  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):460–470

    Article  CAS  PubMed  Google Scholar 

  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 129:255–265

    Article  CAS  PubMed  Google Scholar 

  95. Lesley J, Hascall VC, Tammi M, Hyman R (2000) Hyaluronan binding by cell surface CD44. J Biol Chem 275(35):26967–26975

    CAS  PubMed  Google Scholar 

  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 185:381–385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):ra116

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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):5283–5295

    Article  CAS  PubMed  Google Scholar 

  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):1193–1199

    Article  CAS  PubMed  Google Scholar 

  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):3288

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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 269:8878–8884

    CAS  PubMed  Google Scholar 

  102. Davis SJ, van der Merwe PA (2006) The kinetic-segregation model: TCR triggering and beyond. Nat Immunol 7(8):803–809

    Article  CAS  PubMed  Google Scholar 

  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):493–497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):477–486

    Article  CAS  PubMed  Google Scholar 

  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):539–553

    Article  CAS  PubMed  Google Scholar 

  106. Arandjelovic S, Ravichandran KS (2015) Phagocytosis of apoptotic cells in homeostasis. Nat Immunol 16(9):907–917

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):11590–11594

    Article  CAS  PubMed  Google Scholar 

  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):1369–1380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):1305–1315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):451–462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Zhang Y, Du G (2009) Phosphatidic acid signaling regulation of Ras superfamily of small guanosine triphosphatases. Biochim Biophys Acta 1791(9):850–855

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Nag S, Larsson M, Robinson RC, Burtnick LD (2013) Gelsolin: the tail of a molecular gymnast. Cytoskeleton (Hoboken) 70(7):360–384

    Article  CAS  Google Scholar 

  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):101–112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Mizuno K (2013) Signaling mechanisms and functional roles of cofilin phosphorylation and dephosphorylation. Cell Signal 25(2):457–469

    Article  CAS  PubMed  Google Scholar 

  115. Hoppe AD, Swanson JA (2004) Cdc42, Rac1, and Rac2 display distinct patterns of activation during phagocytosis. Mol Biol Cell 15(8):3509–3519

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Banjade S, Rosen MK (2014) Phase transitions of multivalent proteins can promote clustering of membrane receptors. Elife 3. https://doi.org/10.7554/eLife.04123

  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):2825–2830

    Article  CAS  PubMed  Google Scholar 

  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):2035–2046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):4307–4318

    CAS  PubMed  Google Scholar 

  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):1299–1310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):815–824

    Article  CAS  PubMed  Google Scholar 

  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):6087–6097

    Article  CAS  PubMed  Google Scholar 

  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):1215–1226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):305–316

    Article  CAS  PubMed  Google Scholar 

  125. Koh AL, Sun CX, Zhu F, Glogauer M (2005) The role of Rac1 and Rac2 in bacterial killing. Cell Immunol 235(2):92–97

    Article  CAS  PubMed  Google Scholar 

  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 e496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 6:8623

    Article  CAS  PubMed  Google Scholar 

  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):697–706

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

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.

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Authors and Affiliations

  1. Program in Cell Biology, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, Canada

    Sivakami M. Mylvaganam, Sergio Grinstein & Spencer A. Freeman

  2. Department of Biochemistry, University of Toronto, Toronto, Canada

    Sivakami M. Mylvaganam & Sergio Grinstein

  3. Keenan Research Centre of the Li Ka Shing Knowledge Institute, St. Michael’s Hospital, 290 Victoria Street, Toronto, Canada

    Sergio Grinstein

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  1. Sivakami M. Mylvaganam
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  2. Sergio Grinstein
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  3. Spencer A. Freeman
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Correspondence to Spencer A. Freeman.

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This article is a contribution to the special issue on Professional and Nonprofessional Phagocytes and Diseases - Guest Editor: Toru Miyazaki

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Mylvaganam, S.M., Grinstein, S. & Freeman, S.A. Picket-fences in the plasma membrane: functions in immune cells and phagocytosis. Semin Immunopathol 40, 605–615 (2018). https://doi.org/10.1007/s00281-018-0705-x

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  • DOI: https://doi.org/10.1007/s00281-018-0705-x

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