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PMID: 17442887 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

MTOC reorientation occurs during FcgammaR-mediated phagocytosis in macrophages.

Molecular biology of the cell ·Vol. 18 ·No. 7 ·2007-07-00 ·Pages 2389-99

Eng EW, Bettio A, Ibrahim J, Harrison RE

Abstract

Cell polarization is essential for targeting signaling elements and organelles to active plasma membrane regions. In a few specialized cell types, cell polarity is enhanced by reorientation of the MTOC and associated organelles toward dynamic membrane sites. Phagocytosis is a highly polarized process whereby particles >0.5 microm are internalized at stimulated regions on the cell surface of macrophages. Here we provide detailed evidence that the MTOC reorients toward the site of particle internalization during phagocytosis. We visualized MTOC proximity to IgG-sRBCs in fixed RAW264.7 cells, during live cell imaging using fluorescent chimeras to label the MTOC and using frustrated phagocytosis assays. MTOC reorientation in macrophages is initiated by FcgammaR ligation and is complete within 1 h. Polarization of the MTOC toward the phagosome requires the MT cytoskeleton and dynein motor activity. cdc42, PI3K, and mPAR-6 are all important signaling molecules for MTOC reorientation during phagocytosis. MTOC reorientation was not essential for particle internalization or phagolysosome formation. However Golgi reorientation in concert with MTOC reorientation during phagocytosis implicates MTOC reorientation in antigen processing events in macrophages.

MeSH Terms
Actins/metabolism Adaptor Proteins, Signal Transducing/metabolism Animals Cell Polarity Dyneins/metabolism Golgi Apparatus/metabolism Macrophages/cytology,metabolism Mice Microtubule-Organizing Center/metabolism Microtubules/metabolism Models, Biological Phagocytosis Phagosomes/metabolism Phosphatidylinositol 3-Kinases/metabolism Receptors, Fc/metabolism Sheep Signal Transduction cdc42 GTP-Binding Protein/metabolism
Chemicals
Actins Adaptor Proteins, Signal Transducing Par6 protein, mouse Receptors, Fc Phosphatidylinositol 3-Kinases Dyneins cdc42 GTP-Binding Protein
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Eng Edward W
Department of Cell and Systems Biology, University of Toronto at Scarborough, Toronto, Ontario, Canada.
Bettio Adam
Ibrahim John
Harrison Rene E
References (56)
56 references, click to expand
  1. Effects of immobilized immune complexes on Fc- and complement-receptor function in resident and thioglycollate-elicited mouse peritoneal macrophages.
    J Exp Med. 1979 Sep 19;150(3):607-21 PMID: 383878
  2. GFP-golvesin constructs to study Golgi tubulation and post-Golgi vesicle dynamics in phagocytosis.
    Eur J Cell Biol. 2004 Jul;83(6):297-303 PMID: 15511087
  3. Distribution of microtubule organizing centers in migrating sheets of endothelial cells.
    J Cell Biol. 1981 Nov;91(2 Pt 1):589-94 PMID: 7309800
  4. Polarization of the Golgi apparatus and the microtubule-organizing center in cultured fibroblasts at the edge of an experimental wound.
    Proc Natl Acad Sci U S A. 1982 Apr;79(8):2603-7 PMID: 7045867
  5. Membrane insertion at the leading edge of motile fibroblasts.
    Proc Natl Acad Sci U S A. 1983 Mar;80(5):1367-71 PMID: 6298789
  6. Microtubule-organizing centers and cell migration: effect of inhibition of migration and microtubule disruption in endothelial cells.
    J Cell Biol. 1983 May;96(5):1266-72 PMID: 6341378
  7. Location of actin, myosin, and microtubular structures during directed locomotion of Dictyostelium amebae.
    J Cell Biol. 1984 Feb;98(2):382-90 PMID: 6319425
  8. Reorientation of the microtubule-organizing center and the Golgi apparatus in cloned cytotoxic lymphocytes triggered by binding to lysable target cells.
    J Immunol. 1984 Nov;133(5):2762-6 PMID: 6384372
  9. Reorientation of the Golgi apparatus and the microtubule-organizing center inside macrophages subjected to a chemotactic gradient.
    Cell Motil. 1985;5(1):17-29 PMID: 3978702
  10. Reorientation and fusion of cytotoxic T lymphocyte granules after interaction with target cells as determined by high resolution cinemicrography.
    J Immunol. 1986 Jan;136(2):377-82 PMID: 3510248
  11. The phagocytosis of yeast cells by monocytes: effects of colchicine, beta-lumicolchicine, and gamma-lumicolchicine.
    Lymphology. 1986 Sep;19(3):130-5 PMID: 3537551
  12. The directed migration of eukaryotic cells.
    Annu Rev Cell Biol. 1986;2:337-65 PMID: 3548771
  13. The reorientation of the Golgi apparatus and the microtubule-organizing center in the cytotoxic effector cell is a prerequisite in the lysis of bound target cells.
    J Mol Cell Immunol. 1985;2(1):37-49 PMID: 3880506
  14. Polarized expression of cytokines in cell conjugates of helper T cells and splenic B cells.
    Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):775-9 PMID: 1825141
  15. T-cell effector functions: mechanisms for delivery of cytotoxicity and help.
    Annu Rev Cell Biol. 1991;7:479-504 PMID: 1839711
  16. The macrophage capacity for phagocytosis.
    J Cell Sci. 1992 Apr;101 ( Pt 4):907-13 PMID: 1527185
  17. The distribution of centrosomes in migrating endothelial cells during wound healing in situ.
    Biochem Cell Biol. 1992 Oct-Nov;70(10-11):1135-41 PMID: 1297337
  18. Regulation of the polarization of T cells toward antigen-presenting cells by Ras-related GTPase CDC42.
    Proc Natl Acad Sci U S A. 1995 May 23;92(11):5027-31 PMID: 7761442
  19. Molecular characterization of the 50-kD subunit of dynactin reveals function for the complex in chromosome alignment and spindle organization during mitosis.
    J Cell Biol. 1996 Feb;132(4):617-33 PMID: 8647893
  20. Molecular requirements for bi-directional movement of phagosomes along microtubules.
    J Cell Biol. 1997 Apr 7;137(1):113-29 PMID: 9105041
  21. Overexpression of the dynamitin (p50) subunit of the dynactin complex disrupts dynein-dependent maintenance of membrane organelle distribution.
    J Cell Biol. 1997 Oct 20;139(2):469-84 PMID: 9334349
  22. Visualization of peptides derived from liposome-encapsulated proteins in the trans-Golgi area of macrophages.
    Immunol Lett. 1997 Nov;59(2):99-105 PMID: 9373218
  23. Cytoskeletal polarization of T cells is regulated by an immunoreceptor tyrosine-based activation motif-dependent mechanism.
    J Cell Biol. 1998 Feb 23;140(4):861-71 PMID: 9472038
  24. Dynein- and microtubule-mediated translocation of adenovirus serotype 5 occurs after endosomal lysis.
    Hum Gene Ther. 2000 Jan 1;11(1):151-65 PMID: 10646647
  25. Phagosomes acquire nascent and recycling class II MHC molecules but primarily use nascent molecules in phagocytic antigen processing.
    J Immunol. 2000 May 15;164(10):5103-12 PMID: 10799867
  26. Restricted accumulation of phosphatidylinositol 3-kinase products in a plasmalemmal subdomain during Fc gamma receptor-mediated phagocytosis.
    J Cell Biol. 2001 Jun 25;153(7):1369-80 PMID: 11425868
  27. Integrin-mediated activation of Cdc42 controls cell polarity in migrating astrocytes through PKCzeta.
    Cell. 2001 Aug 24;106(4):489-98 PMID: 11525734
  28. Cdc42, dynein, and dynactin regulate MTOC reorientation independent of Rho-regulated microtubule stabilization.
    Curr Biol. 2001 Oct 2;11(19):1536-41 PMID: 11591323
  29. Phagocytosis and innate immunity.
    Curr Opin Immunol. 2002 Feb;14(1):136-45 PMID: 11790544
  30. Dynamic polarization of the microtubule cytoskeleton during CTL-mediated killing.
    Immunity. 2002 Jan;16(1):111-21 PMID: 11825570
  31. Evolutionary conservation of microtubule-capture mechanisms.
    Nat Rev Mol Cell Biol. 2002 Apr;3(4):296-304 PMID: 11994749
  32. Rac1 and Cdc42 capture microtubules through IQGAP1 and CLIP-170.
    Cell. 2002 Jun 28;109(7):873-85 PMID: 12110184
  33. Endoplasmic reticulum-mediated phagocytosis is a mechanism of entry into macrophages.
    Cell. 2002 Jul 12;110(1):119-31 PMID: 12151002
  34. Phagocytosis and the microtubule cytoskeleton.
    Biochem Cell Biol. 2002;80(5):509-15 PMID: 12440692
  35. Cytoplasmic linker proteins promote microtubule rescue in vivo.
    J Cell Biol. 2002 Nov 25;159(4):589-99 PMID: 12446741
  36. Microtubule involvement in NIH 3T3 Golgi and MTOC polarity establishment.
    J Cell Sci. 2003 Feb 15;116(Pt 4):743-56 PMID: 12538774
  37. Differential role of actin, clathrin, and dynamin in Fc gamma receptor-mediated endocytosis and phagocytosis.
    J Biol Chem. 2003 Jan 31;278(5):3331-8 PMID: 12424246
  38. Cdc42 regulates GSK-3beta and adenomatous polyposis coli to control cell polarity.
    Nature. 2003 Feb 13;421(6924):753-6 PMID: 12610628
  39. Phagosomes fuse with late endosomes and/or lysosomes by extension of membrane protrusions along microtubules: role of Rab7 and RILP.
    Mol Cell Biol. 2003 Sep;23(18):6494-506 PMID: 12944476
  40. Fcgamma-receptors induce Mac-1 (CD11b/CD18) mobilization and accumulation in the phagocytic cup for optimal phagocytosis.
    J Biol Chem. 2003 Nov 14;278(46):45720-9 PMID: 12941957
  41. The uniformity of phagosome maturation in macrophages.
    J Cell Biol. 2004 Jan 19;164(2):185-94 PMID: 14718518
  42. Functional microtubules are required for antigen processing by macrophages and dendritic cells.
    Immunol Lett. 2004 Aug 15;95(1):13-24 PMID: 15325793
  43. Selective phagocytic paralysis induced by immobilized immune complexes.
    J Exp Med. 1975 Oct 1;142(4):827-38 PMID: 1185106
  44. Structural analysis of human neutrophil migration. Centriole, microtubule, and microfilament orientation and function during chemotaxis.
    J Cell Biol. 1977 Dec;75(3):666-93 PMID: 562885
  45. Size of IgG-opsonized particles determines macrophage response during internalization.
    Exp Cell Res. 1998 Jul 10;242(1):265-73 PMID: 9665824
  46. Identification of two distinct mechanisms of phagocytosis controlled by different Rho GTPases.
    Science. 1998 Nov 27;282(5394):1717-21 PMID: 9831565
  47. A requirement for phosphatidylinositol 3-kinase in pseudopod extension.
    J Biol Chem. 1999 Jan 15;274(3):1240-7 PMID: 9880492
  48. Access of soluble antigens to the endoplasmic reticulum can explain cross-presentation by dendritic cells.
    Nat Immunol. 2005 Jan;6(1):107-13 PMID: 15592474
  49. Nuclear movement regulated by Cdc42, MRCK, myosin, and actin flow establishes MTOC polarization in migrating cells.
    Cell. 2005 May 6;121(3):451-63 PMID: 15882626
  50. Centriolin anchoring of exocyst and SNARE complexes at the midbody is required for secretory-vesicle-mediated abscission.
    Cell. 2005 Oct 7;123(1):75-87 PMID: 16213214
  51. Quantitative and dynamic assessment of the contribution of the ER to phagosome formation.
    Cell. 2005 Oct 7;123(1):157-70 PMID: 16213220
  52. The many roads to cross-presentation.
    J Exp Med. 2005 Nov 21;202(10):1313-8 PMID: 16287713
  53. Regulation of microtubules by Rho GTPases in migrating cells.
    Novartis Found Symp. 2005;269:106-16; discussion 116-26, 223-30 PMID: 16358406
  54. Centrosome polarization delivers secretory granules to the immunological synapse.
    Nature. 2006 Sep 28;443(7110):462-5 PMID: 17006514
  55. Recruitment of dynein to the Jurkat immunological synapse.
    Proc Natl Acad Sci U S A. 2006 Oct 3;103(40):14883-8 PMID: 16990435
  56. Polarization of endocytosis and receptor topography on cultured macrophages.
    J Cell Biol. 1980 Jul;86(1):199-211 PMID: 7419574
Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e06-12-1128
Published
2007-07-00
Epub
2007-00-18
Pages
2389-99
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC1924806
Subset
IM
External Links
PubMed source DOI: 10.1091/mbc.e06-12-1128 PMC Full Text View journal details
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