Biogenesis of phagolysosomes proceeds through a sequential series of interactions with the endocytic apparatus
Open accessAbstract
We have examined the modifications occurring during the transformation of phagosomes into phagolysosomes in J-774 macrophages. The use of low density latex beads as markers of phagosomes (latex bead compartments, LBC) allowed the isolation of these organelles by flotation on a simple sucrose gradient. Two-dimensional gel electrophoresis, immunocytochemistry, and biochemical assays have been used to characterize the composition of LBC at different time points after their formation, as well as their interactions with the organelles of the endocytic pathway. Our results show that LBC acquire and lose various markers during their transformation into phagolysosomes. Among these are members of the rab family of small GTPases as well as proteins of the lamp family. The transfer of the LBC of lamp 2, a membrane protein associated with late endocytic structures, was shown to be microtubule dependent. Video-microscopy showed that newly formed phagosomes were involved in rapid multiple contacts with late components of the endocytic pathway. Collectively, these observations suggest that phagolysosome formation is a highly dynamic process that involves the gradual and regulated acquisition of markers from endocytic organelles.
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The movement of phagosomes along microtubules likely facilitates the interaction of phagosomes with endosomes and lysosomes.
“Earlier studies on the phagocytosis of latex beads by macrophages concluded that the movement of the phagosomes along microtubules likely facilitates the interaction of phagosomes with endosomes and lysosomes (Rabinowitz et al., 1992; Desjardins et al., 1994).”
From Microtubule motors transport phagosomes in the RPE, and lack of KLC1 leads to AMD-like pathogenesis (2015) · cites this paper as Desjardins et al., 1994
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Cites
Kornfeld, S. A., & Mellman, I. (1989) · Annual Review of Cell Biology · doi:10.1146/annurev.cb.05.110189.002411 · Cited by 1,593 · see citing works
A new method of preparing gold probes for multiple-labeling cytochemistry.
Slot, J. W., & Geuze, H. J. (1985) · PubMed · Cited by 1,419 · see citing works
The small GTPase rab5 functions as a regulatory factor in the early endocytic pathway
Bucci, C., Parton, R. G., Mather, I. H., Stunnenberg, H. G., Simons, K., Hoflack, B., & Zerial, M. (1992) · Cell · doi:10.1016/0092-8674(92)90306-w · Cited by 1,370 · see citing works
Self-citationLocalization of low molecular weight GTP binding proteins to exocytic and endocytic compartments
Chavrier, P., Parton, R. G., Hauri, H. P., Simons, K., & Zerial, M. (1990) · Cell · doi:10.1016/0092-8674(90)90369-p · Cited by 1,166 · see citing works
Self-citationrab5 controls early endosome fusion in vitro
Gorvel, J., Chavrier, P., Zerial, M., & Gruenberg, J. E. (1991) · Cell · doi:10.1016/0092-8674(91)90316-q · Cited by 1,094 · see citing works
The Cellular Functions of Small GTP-Binding Proteins
Hall, A. (1990) · Science · doi:10.1126/science.2116664 · Cited by 866 · see citing works
Gruenberg, J. E., Griffiths, G. W., & Howell, K. E. (1989) · The Journal of Cell Biology · doi:10.1083/jcb.108.4.1301 · Cited by 586 · see citing works
Self-citationIdentification of two lysosomal membrane glycoproteins.
Chen, J. W., Murphy, T. L., Willingham, M. C., Pastan, I. H., & August, J. T. (1985) · The Journal of Cell Biology · doi:10.1083/jcb.101.1.85 · Cited by 485 · see citing works
Huber, L. A., Pimplikar, S. W., Parton, R. G., Virta, H., Zerial, M., & Simons, K. (1993) · The Journal of Cell Biology · doi:10.1083/jcb.123.1.35 · Cited by 466 · see citing works
Self-citationOn the preparation of cryosections for immunocytochemistry
Griffiths, G. W., McDowall, A. W., Back, R., & Dubochet, J. (1984) · Journal of Ultrastructure Research · doi:10.1016/s0022-5320(84)80024-6 · Cited by 461 · see citing works
Self-citationJoiner, K. A., Fuhrman, S. A., Miettinen, H. M., Kasper, L. H., & Mellman, I. (1990) · Science · doi:10.1126/science.2200126 · Cited by 447 · see citing works
Rab GTPases in vesicular transport
Zerial, M., & Stenmark, H. (1993) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(93)90130-i · Cited by 382 · see citing works
Macropinosome maturation and fusion with tubular lysosomes in macrophages.
Racoosin, E. L., & Swanson, J. A. (1993) · The Journal of Cell Biology · doi:10.1083/jcb.121.5.1011 · Cited by 335 · see citing works
The small GTP-binding protein rab4 is associated with early endosomes.
van der Sluijs, P., Hull, M. J., Zahraoui, A., Tavitian, A., Goud, B., & Mellman, I. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.14.6313 · Cited by 288 · see citing works
GTP-binding proteins in intracellular transport
Pfeffer, S. R. (1992) · Trends in Cell Biology · doi:10.1016/0962-8924(92)90161-f · Cited by 278 · see citing works
Wandinger‐Ness, A., Bennett, M. K., Antony, C., & Simons, K. (1990) · The Journal of Cell Biology · doi:10.1083/jcb.111.3.987 · Cited by 274 · see citing works
Rabinowitz, S., Horstmann, H., Gordon, S., & Griffiths, G. (1992) · The Journal of Cell Biology · doi:10.1083/jcb.116.1.95 · Cited by 271 · see citing works
Self-citationAxonal and dendritic endocytic pathways in cultured neurons.
Parton, R. G., Simons, K., & Dotti, C. G. (1992) · The Journal of Cell Biology · doi:10.1083/jcb.119.1.123 · Cited by 269 · see citing works
Self-citationGeisow, M. J., Hart, P. D., & Young, M. R. (1981) · The Journal of Cell Biology · doi:10.1083/jcb.89.3.645 · Cited by 248 · see citing works
Barriocanal, J. G., Bonifacino, J. S., Yuan, L. C., & Sandoval, I. V. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)66630-x · Cited by 217 · see citing works
Alterations in the protein composition of maturing phagosomes.
Pitt, A., Mayorga, L. S., Stahl, P. D., & Schwartz, A. L. (1992) · Journal of Clinical Investigation · doi:10.1172/jci116077 · Cited by 202 · see citing works
Kinetics of intracellular transport and sorting of lysosomal membrane and plasma membrane proteins.
Green, S. A., Zimmer, K. ‐., Griffiths, G. W., & Mellman, I. (1987) · The Journal of Cell Biology · doi:10.1083/jcb.105.3.1227 · Cited by 200 · see citing works
Self-citationMüller, W. A., Steinman, R. M., & Cohn, Z. A. (1980) · The Journal of Cell Biology · doi:10.1083/jcb.86.1.304 · Cited by 164 · see citing works
Three-dimensional structure of endosomes in BHK-21 cells.
Marsh, M., Griffiths, G., Dean, G. E., Mellman, I., & Helenius, A. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.9.2899 · Cited by 162 · see citing works
Self-citationHart, P. D., & Young, M. R. (1991) · The Journal of Experimental Medicine · doi:10.1084/jem.174.4.881 · Cited by 154 · see citing works
van der Sluijs, P., Hull, M. J., Huber, L. A., Mâle, P., Goud, B., & Mellman, I. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05538.x · Cited by 148 · see citing works
Self-citationPHAGOCYTOSIS OF LATEX BEADS BY ACANTHAMOEBA CASTELLANII (NEFF)
Wetzel, M. G., & Korn, E. D. (1969) · The Journal of Cell Biology · doi:10.1083/jcb.43.1.90 · Cited by 143 · see citing works
Fusion of newly formed phagosomes with endosomes in intact cells and in a cell-free system.
Mayorga, L. S., Bertini, F., & Stahl, P. D. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)38147-x · Cited by 139 · see citing works
Hubbard, A. L., & Cohn, Z. A. (1975) · The Journal of Cell Biology · doi:10.1083/jcb.64.2.461 · Cited by 139 · see citing works
Genetic and biochemical analysis of vesicular traffic in yeast
Schekman, R. W. (1992) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(92)90076-o · Cited by 137 · see citing works
Celis, J. E., Rasmussen, H. H., Madsen, P., et al. (1992) · Electrophoresis · doi:10.1002/elps.11501301198 · Cited by 125 · see citing works
The complexity of the Rab and Rho GTP-binding protein subfamilies revealed by a PCR cloning approach
Chavrier, P., Simons, K., & Zerial, M. (1992) · Gene · doi:10.1016/0378-1119(92)90387-5 · Cited by 120 · see citing works
Phagosome-lysosome fusion. Characterization of intracellular membrane fusion in mouse macrophages.
Kielian, M. C., & Cohn, Z. A. (1980) · The Journal of Cell Biology · doi:10.1083/jcb.85.3.754 · Cited by 113 · see citing works
Transport of phagosomal components to an endosomal compartment.
Pitt, A., Mayorga, L. S., Schwartz, A. L., & Stahl, P. D. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)48468-2 · Cited by 108 · see citing works
Galactose transfer to endogenous acceptors within Golgi fractions of rat liver.
Bergeron, J. J. M., Rachubinski, R. A., Sikstrom, R., et al. (1982) · The Journal of Cell Biology · doi:10.1083/jcb.92.1.139 · Cited by 104 · see citing works
Hart, P. D., Young, M. R., Gordon, A., et al. (1987) · The Journal of Experimental Medicine · doi:10.1084/jem.166.4.933 · Cited by 104 · see citing works
Muller, W. A., Steinman, R. M., & Cohn, Z. A. (1980) · The Journal of Cell Biology · doi:10.1083/jcb.86.1.292 · Cited by 93 · see citing works
Regulation of intracellular membrane transport
Grüenberg, J., & Clague, M. J. (1992) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(92)90077-p · Cited by 73 · see citing works
Hart, P. D., Young, M. R., Jordan, M. M., Perkins, W. J., & Geisow, M. J. (1983) · The Journal of Experimental Medicine · doi:10.1084/jem.158.2.477 · Cited by 68 · see citing works
Wang, Y. L., & Goren, M. B. (1987) · The Journal of Cell Biology · doi:10.1083/jcb.104.6.1749 · Cited by 68 · see citing works
Accumulation of indigestible substances reduces fusion competence of macrophage lysosomes
Montgomery, R. R., Webster, P. C., & Mellman, I. (1991) · The Journal of Immunology · doi:10.4049/jimmunol.147.9.3087 · Cited by 53 · see citing works
Lang, T., de Chastellier, C., Ryter, A., & Thilo, L. (1988) · PubMed · Cited by 39 · see citing works
Modified lysosomal compartment as carrier of slowly and non-degradable tracers in macrophages.
Tassin, M. T., Lang, T., Antoine, J. C., Hellio, R., & Ryter, A. (1990) · PubMed · Cited by 33 · see citing works
Small GTP-Binding Proteins on Rat Liver Lysosomal Membranes.
Sai, Y., & Ohkuma, S. (1992) · Cell Structure and Function · doi:10.1247/csf.17.363 · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Rab GTPases as coordinators of vesicle traffic
Stenmark, H. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2728 · Cited by 3,413 · see citing works
Mechanisms of phagocytosis in macrophages
Aderem, A., & Underhill, D. M. (1999) · Annual Review of Immunology · doi:10.1146/annurev.immunol.17.1.593 · Cited by 2,854 · see citing works
Nanotubular Highways for Intercellular Organelle Transport
Rustom, A., Saffrich, R., Markovic, I., Walther, P., & Gerdes, H.-H. (2004) · Science · doi:10.1126/science.1093133 · Cited by 2,038 · see citing works
Antimicrobial mechanisms of phagocytes and bacterial evasion strategies
Flannagan, R. S., Cosío, G., & Grinstein, S. (2009) · Nature Reviews Microbiology · doi:10.1038/nrmicro2128 · Cited by 947 · see citing works
Martinez, J., Malireddi, R. K. S., Lu, Q., Cunha, L. D., Pelletier, S., Gingras, S., Orchard, R., Guan, J.-L., Tan, H., Peng, J., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3192 · Cited by 758 · see citing works
RetractedJanus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis
Sierra, A., Abiega, O., Shahraz, A., & Neumann, H. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00006 · Cited by 574 · see citing works
Activation of antibacterial autophagy by NADPH oxidases
Huang, J., Canadien, V., Lam, G. Y., Steinberg, B. E., Dinauer, M. C., Magalhaes, M. A. O., Glogauer, M., Grinstein, S., & Brumell, J. H. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0811045106 · Cited by 556 · see citing works
A Role for the ATP7A Copper-transporting ATPase in Macrophage Bactericidal Activity
White, C., Lee, J., Kambe, T., Fritsche, K., & Petris, M. J. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.070201 · Cited by 524 · see citing works
The phagosome: compartment with a license to kill
Haas, A. (2007) · Traffic · doi:10.1111/j.1600-0854.2006.00531.x · Cited by 450 · see citing works
Gruenheid, S., Pinner, E., Desjardins, M., & Gros, P. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.4.717 · Cited by 428 · see citing works
Self-citationSturgill‐Koszycki, S., Schaible, U. E., & Russell, D. G. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb01088.x · Cited by 356 · see citing works
Henault, J., Martinez, J., Riggs, J. M., Tian, J., Mehta, P., Clarke, L., Sasai, M., Latz, E., Brinkmann, M. M., Iwasaki, A., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.09.014 · Cited by 348 · see citing works
Phagocytosis and Intracellular Fate of<i>Aspergillus fumigatus</i>Conidia in Alveolar Macrophages
Ibrahim-Granet, O., Philippe, B., Boleti, H., Boisvieux-Ulrich, E., Grenet, D., Stern, M., & Latgé, J. P. (2003) · Infection and Immunity · doi:10.1128/iai.71.2.891-903.2003 · Cited by 277 · see citing works
The origins of phagocytosis and eukaryogenesis
Yutin, N., Wolf, M. Y., Wolf, Y. I., & Koonin, E. V. (2009) · Biology Direct · doi:10.1186/1745-6150-4-9 · Cited by 247 · see citing works
“An early phagosome has been reported to fuse, consecutively, with the early/ sorting/recycling endosome, late endosome and lisosome [20,33].”
BackgroundHackam, D. J., Rotstein, O. D., Zhang, W.-J., Gruenheid, S., Gros, P., & Grinstein, S. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.2.351 · Cited by 202 · see citing works
Ca2+ and synaptotagmin VII–dependent delivery of lysosomal membrane to nascent phagosomes
Czibener, C., Sherer, N. M., Becker, S. M., Pypaert, M., Hui, E., Chapman, E. R., Mothes, W., & Andrews, N. W. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200605004 · Cited by 165 · see citing works
Wasylnka, J. A., & Moore, M. M. (2003) · Journal of Cell Science · doi:10.1242/jcs.00329 · Cited by 161 · see citing works
Ip, W. K. E., Sokolovska, A., Charriere, G. M., Boyer, L., Dejardin, S., Cappillino, M. P., Yantosca, L. M., Takahashi, K., Moore, K. J., Lacy-Hulbert, A., et al. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1000110 · Cited by 148 · see citing works
Fusion, fission, and secretion during phagocytosis
Huynh, K. K., Kay, J. G., Stow, J. L., & Grinstein, S. (2007) · Physiology · doi:10.1152/physiol.00028.2007 · Cited by 105 · see citing works
Myosin Va bound to phagosomes binds to F-actin and delays microtubule-dependent motility
Al-Haddad, A., Shonn, M. A., Redlich, B., Blocker, A., Burkhardt, J. K., Yu, H., Hammer, J. A., Weiss, D. G., Steffen, W., Griffiths, G., et al. (2001) · Molecular Biology of the Cell · doi:10.1091/mbc.12.9.2742 · Cited by 102 · see citing works
Self-citationProteomics Fingerprinting of Phagosome Maturation and Evidence for the Role of a Gα during Uptake
Gotthardt, D., Blancheteau, V., Bosserhoff, A., Ruppert, T., Delorenzi, M., & Soldati, T. (2006) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m600113-mcp200 · Cited by 98 · see citing works
Microtubule motors transport phagosomes in the RPE, and lack of KLC1 leads to AMD-like pathogenesis
Jiang, M., Esteve-Rudd, J., Lopes, V. S., Diemer, T., Lillo, C., Rump, A., & Williams, D. S. (2015) · Journal of Cell Biology · doi:10.1083/jcb.201410112 · Cited by 85 · see citing works
Microtubule-associated protein-dependent binding of phagosomes to microtubules
Blocker, A., Severin, F. F., Habermann, A., Hyman, A. A., Griffiths, G., & Burkhardt, J. K. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.7.3803 · Cited by 81 · see citing works
Self-citationCuellar-Mata, P., Jabado, N., Liu, J., Furuya, W., Finlay, B. B., Gros, P., & Grinstein, S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m105508200 · Cited by 79 · see citing works
Wavre-Shapton, S. T., Meschede, I. P., Seabra, M. C., & Futter, C. E. (2014) · Journal of Cell Science · doi:10.1242/jcs.154757 · Cited by 60 · see citing works
Brumell, J. H., Howard, J. C., Craig, K., Grinstein, S., Schreiber, A. D., & Tyers, M. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.6.3388 · Cited by 54 · see citing works
Clearance of apoptotic corpses
Fullard, J. F., Kale, A., & Baker, N. E. (2009) · Apoptosis · doi:10.1007/s10495-009-0335-9 · Cited by 46 · see citing works
Esteve-Rudd, J., Hazim, R. A., Diemer, T., Paniagua, A. E., Volland, S., Umapathy, A., & Williams, D. S. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1709211115 · Cited by 42 · see citing works
- Authors
- Desjardins, M., Huber, L., Parton, R., & Griffiths, G.
- Affiliations
- European Molecular Biology Laboratory (DE)
- European Molecular Biology Laboratory, Cell Biology Program, Heidelberg, Germany.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 1994-03-01
- Volume
- 124
- Issue
- 5
- Pages
- 677-688
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2119957
- OpenAlex
- W2049288737
- Cited by
- 673
- References
- 44
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 10 · 2023: 12 · 2022: 14 · 2021: 12 · 2020: 12 · 2019: 16 · 2018: 10 · 2017: 16 · 2016: 12 · 2015: 14 · 2014: 24 · 2013: 26 · 2012: 18
- FWCI
- 8.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- phagolysosome biogenesis, phagosome maturation, endocytic pathway, Rab GTPases, LAMP2, microtubule transport, late endosomes
- MeSH terms
- Animals, Cell Fractionation, Cell Line, Centrifugation, Density Gradient, Endocytosis, Guanosine Triphosphate, Immunohistochemistry, Kinetics, Lysosomes, Macrophages, Methionine, Microscopy, Electron, Microtubules, Phagocytosis, Proteins, Protein Biosynthesis, Video Recording, Immunoblotting, Electrophoresis, Gel, Two-Dimensional, Organelles, Mice
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