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The regulation of phagosome maturation in Dictyostelium

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Abstract

Macropinocytosis (fluid uptake) and phagocytosis (particle uptake) are processes that result in the formation of intracellular membrane enclosed vacuoles termed macropinosomes and phagosomes, respectively. Macropinosomes and phagosomes are modified by fission and fusion reactions with the endo-lysosomal pathway that eventually transform these vacuoles into a lysosomal environment. Many human bacterial pathogens, including species of Mycobacteria, Legionella, and Chlamydia, are thought to survive by disrupting the normal membrane trafficking events that usually result in the formation of phago-lysosomes and death of the microorganism. In addition, a number of important pathogens facilitate homotypic phagosome fusion in order to generate an intracellular environment conducive for survival. A greater understanding of the regulation of phagosomal maturation and fusion will be critical in designing new therapies to treat infections caused by intracellular pathogens. The genetically tractable phagocyte, D. discoideum, has proven extremely useful in dissecting the signaling pathways regulating macropinocytosis, phagocytosis, phagosomal maturation and phagosome–phagosome fusion. A body of knowledge has accumulated and demonstrates important roles for Rab GTPases, the cytoskeleton, phosphoinositide metabolism and pH regulation in regulating phagosome maturation. This review will summarize the current state of knowledge.

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References

  • Allen LA, Schlesinger LS and Kang B (2000) Virulent strains of Helicobacter pylori demonstrate delayed phagocytosis and stimulate homotypic phagosome fusion in macrophages. J Exp Med 191(1): 115–128.

    Google Scholar 

  • Aubry L, Klein G, Martiel JL and Satre M (1993) Kinetics of endosomal pH evolution in Dictyostelium discoideum amoebae. Study by fluorescence spectroscopy. J Cell Sci 105(Pt 3): 861–866.

    Google Scholar 

  • Bogdanovic A, Bennett N, Kieffer S, Louwagie M, Morio T, Garin J, Satre M and Bruckert F (2002) Syntaxin 7, syntaxin 8, Vti1 and VAMP7 (vesicle-associated membrane protein 7) form an active SNARE complex for early macropinocytic compartment fusion in Dictyostelium discoideum. Biochem J 368(Pt 1): 29–39.

    Google Scholar 

  • Bogdanovic A, Bruckert F, Morio T and Satre M (2000) A syntaxin 7 homologue is present in Dictyostelium discoideum endosomes and controls their homotypic fusion. J Biol Chem 275(47): 36,691–36,697.

    Google Scholar 

  • Buczynski G, Grove B, Nomura A, Kleve M, Bush J, Firtel RA and Cardelli J (1997) Inactivation of two Dictyostelium discoideum genes, DdPIK1 and DdPIK2, encoding proteins related to mammalian phosphatidylinositide 3-kinases, results in defects in endocytosis, lysosome to postlysosome transport, and actin cytoskeleton organization. J Cell Biol 136(6): 1271–1286.

    Google Scholar 

  • Cardelli J (2001) Phagocytosis and macropinocytosis in Dictyostelium: phosphoinositide-based processes, biochemically distinct. Traffic 2(5): 311–320.

    Google Scholar 

  • Clarke M, Kohler J, Arana Q, Liu T, Heuser J and Gerisch G (2002a) Dynamics of the vacuolar H(+)-ATPase in the contractile vacuole complex and the endosomal pathway of Dictyostelium cells. J Cell Sci 115(Pt 14): 2893–2905.

    Google Scholar 

  • Clarke M, Kohler J, Heuser J and Gerisch G (2002b) Endosome fusion and microtubule-based dynamics in the early endocytic pathway of Dictyostelium. Traffic 3(11): 791–800.

    Google Scholar 

  • Cornillon S, Dubois A, Bruckert F, Lefkir Y, Marchetti A, Benghezal M, De Lozanne A, Letourneur F and Cosson P (2002) Two members of the beige/CHS (BEACH) family are involved at different stages in the organization of the endocytic pathway in Dictyostelium. J Cell Sci 115(Pt 4): 737–744.

    Google Scholar 

  • Defacque H, Egeberg M, Antzberger A, Ansorge W, Way M and Griffiths G (2000) Actin assembly induced by polylysine beads or purified phagosomes: quantitation by a new flow cytometry assay. Cytometry 41(1): 46–54.

    Google Scholar 

  • Garin J, Diez R, Kieffer S, Dermine JF, Duclos S, Gagnon E, Sadoul R, Rondeau C and Desjardins M (2001) The phagosome proteome: insight into phagosome functions. J Cell Biol 152(1): 165–180.

    Google Scholar 

  • Gotthardt D, Warnatz HJ, Henschel O, Bruckert F, Schleicher M and Soldati T (2002) High-resolution dissection of phagosome maturation reveals distinct membrane tra.cking phases. Mol Biol Cell 13(10): 3508–3520.

    Google Scholar 

  • Harris E and Cardelli J (2002) RabD, a Dictyostelium Rab14-related GTPase, regulates phagocytosis and homotypic phagosome and lysosome fusion. J Cell Sci 115(Pt 18): 3703–3713.

    Google Scholar 

  • Harris E, Wang N, Wu Wl WL, Weatherford A, De Lozanne A and Cardelli J (2002) Dictyostelium LvsB mutants model the lysosomal defects associated with Chediak-Higashi syndrome. Mol Biol Cell 13(2): 656–669.

    Google Scholar 

  • Hart PD and Young MR (1991) Ammonium chloride, an inhibitor of phagosome-lysosome fusion in macrophages, concurrently induces phagosome-endosome fusion, and opens a novel pathway: studies of a pathogenic mycobacterium and a nonpathogenic yeast. J Exp Med 174(4): 881–889.

    Google Scholar 

  • Insall R, Muller-Taubenberger A, Machesky L, Kohler J, Simmeth E, Atkinson SJ, Weber I and Gerisch G (2001) Dynamics of the Dictyostelium Arp2/3 complex in endocytosis, endocytosis, cytokinesis, and chemotaxis. Cell Motil Cytoskeleton 50(3): 115–128.

    Google Scholar 

  • Jahraus A, Egeberg M, Hinner B, Habermann A, Sackman E, Pralle A, Faulstich H, Rybin V, Defacque H and Griffiths G (2001) ATP-dependent membrane assembly of F-actin facilitates membrane fusion. Mol Biol Cell 12(1): 155–170.

    Google Scholar 

  • Janssen KP and Schleicher M (2001) Dictyostelium discoideum: a genetic model system for the study of professional phagocytes. Profilin, phosphoinositides and the Imp gene family in Dictyostelium. Biochim Biophys Acta 1525(3): 228–233.

    Google Scholar 

  • Jenne N, Rauchenberger R, Hacker U, Kast T and Maniak M (1998) Targeted gene disruption reveals a role for vacuolin B in the late endocytic pathway and exocytosis. J Cell Sci 111(Pt 1): 61–70.

    Google Scholar 

  • Knetsch ML, Schafers N, Horstmann H and Manstein DJ (2001) The Dictyostelium Bcr/Abr-related protein DRG regulates both Rac-and Rab-dependent pathways. Embo J 20(7): 1620–1629.

    Google Scholar 

  • Lee E and Knecht DA (2002) Visualization of actin dynamics during macropinocytosis and exocytosis. Traffic 3(3): 186–192.

    Google Scholar 

  • Majeed M, Krause KH, Clark RA, Kihlstrom E and Stendahl O (1999) Localization of intracellular Ca2+ stores in HeLa cells during infection with Chlamydia trachomatis. J Cell Sci 112(Pt 1): 35–44.

    Google Scholar 

  • Maniak M (2001) Fluid-phase uptake and transit in axenic Dictyostelium cells. Biochim Biophys Acta 1525(3): 197–204.

    Google Scholar 

  • Muller-Taubenberger A, Lupas AN, Li H, Ecke M, Simmeth E and Gerisch G (2001) Calreticulin and calnexin in the endoplasmic reticulumare important for phagocytosis. Embo J 20(23): 6772–6782.

    Google Scholar 

  • Neuhaus EM and Soldati T (1999) Molecular mechanisms of membrane trafficking. What do we learn from Dictyostelium discoideum? Protist 150(3): 235–243.

    Google Scholar 

  • Padgett GA, Reiquam CW, Gorham JR, Henson JB and O'Mary CC (1967) Comparative studies of the Chediak-Higashi syndrome. Am J Pathol 51(4): 553–571.

    Google Scholar 

  • Padh H, Ha J, Lavasa M and Steck TL (1993) A post-lysosomal compartment in Dictyostelium discoideum. J Biol Chem 268(9): 6742–6747.

    Google Scholar 

  • Rauchenberger R, Hacker U, Murphy J, Niewohner J and Maniak M (1997) Coronin and vacuolin identify consecutive stages of a late, actin-coated endocytic compartment in Dictyostelium. Curr Biol 7(3): 215–218.

    Google Scholar 

  • Ravanel K, de Chassey B, Cornillon S, Benghezal M, Zulianello L, Gebbie L, Letourneur F and Cosson P (2001) Membrane sorting in the endocytic and phagocytic pathway of Dictyostelium discoideum. Eur J Cell Biol 80(12): 754–764.

    Google Scholar 

  • Rezabek BL, Rodriguez-Paris JM, Cardelli JA and Chia CP (1997) Phagosomal proteins of Dictyostelium discoideum. J Eukaryot Microbiol 44(4): 284–292.

    Google Scholar 

  • Rupper A and Cardelli J (2001) Regulation of phagocytosis and endophagosomal tra.cking pathways in Dictyostelium discoideum. Biochim Biophys Acta 1525(3): 205–216.

    Google Scholar 

  • Rupper A, Grove B and Cardelli J (2001a) Rab7 regulates phagosome maturation in Dictyostelium. J Cell Sci 114(Pt 13): 2449–2460.

    Google Scholar 

  • Rupper A, Lee K, Knecht D and Cardelli J (2001b) Sequential activities of phosphoinositide 3-kinase, PKB/Aakt, and Rab7 during macropinosome formation in Dictyostelium. Mol Biol Cell 12(9): 2813–2824.

    Google Scholar 

  • Rupper AC, Rodriguez-Paris JM, Grove BD and Cardelli JA (2001c) p110-related PI 3-kinases regulate phagosome-phagosome fusion and phagosomal pH through a PKB/Akt dependent pathway in Dictyostelium. J Cell Sci 114(Pt 7): 1283–1295.

    Google Scholar 

  • Skriwan C, Fajardo M, Hagele S, Horn M, Wagner M, Michel R, Krohne G, Schleicher M, Hacker J and Steinert M (2002) Various bacterial pathogens and symbionts infect the amoeba Dictyostelium discoideum. Int J Med Microbiol 291(8): 615–624.

    Google Scholar 

  • Solomon JM, Rupper A, Cardelli JA and Isberg RR (2000) Intracellular growth of Legionella pneumophila in Dictyostelium discoideum, a system for genetic analysis of host-pathogen interactions. Infect Immun 68(5): 2939–2947.

    Google Scholar 

  • Souza GM, Mehta DP, Lammertz M, Rodriguez-Paris J, Wu R, Cardelli JA and Freeze HH (1997) Dictyostelium lysosomal proteins with different sugar modifications sort to functionally distinct compartments. J Cell Sci 110(Pt 18): 2239–2248.

    Google Scholar 

  • Toyohara A and Inaba K (1989) Transport of phagosomes in mouse peritoneal macrophages. J Cell Sci 94(Pt 1): 143–153.

    Google Scholar 

  • Vieira OV, Botelho RJ and Grinstein S (2002) Phagosome maturation: aging gracefully. Biochem J 366(Pt 3): 689–704.

    Google Scholar 

  • Vieira OV, Botelho RJ, Rameh L, Brachmann SM, Matsuo T, Davidson HW, Schreiber A, Backer JM, Cantley LC and Grinstein S (2001) Distinct roles of class I and class III phosphatidylinositol 3-kinases in phagosome formation and maturation. J Cell Biol 155(1): 19–25.

    Google Scholar 

  • Wickner W (2002) Yeast vacuoles and membrane fusion pathways. Embo J 21(6): 1241–1247.

    Google Scholar 

  • Wickner W and Haas A (2000) Yeast homotypic vacuole fusion: a window on organelle trafficking mechanisms. Annu Rev Biochem 69: 247–275.

    Google Scholar 

  • Zhou K, Takegawa K, Emr SD and Firtel RA (1995) A phosphatidylinositol (PI) kinase gene family in Dictyostelium discoideum: biological roles of putative mammalian p110 and yeast Vps34p PI 3-kinase homologs during growth and development. Mol Cell Biol 15(10): 5645–5656.

    Google Scholar 

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Authors and Affiliations

  1. Department of Microbiology and Immunology, LSU Health Sciences Center, 1501 Kings Highway, Shreveport, LA, 71130, USA

    Damian Duhon & James Cardelli

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  1. Damian Duhon
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  2. James Cardelli
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Duhon, D., Cardelli, J. The regulation of phagosome maturation in Dictyostelium . J Muscle Res Cell Motil 23, 803–808 (2002). https://doi.org/10.1023/A:1024435913949

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