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A role for phosphoinositide 3-kinase in the completion of macropinocytosis and phagocytosis by macrophages
Open accessAbstract
Phosphoinositide 3-kinase (PI 3-kinase) has been implicated in growth factor signal transduction and vesicular membrane traffic. It is thought to mediate the earliest steps leading from ligation of cell surface receptors to increased cell surface ruffling. We show here that inhibitors of PI 3-kinase inhibit endocytosis in macrophages, not by interfering with the initiation of the process but rather by preventing its completion. Consistent with earlier studies, the inhibitors wortmannin and LY294002 inhibited fluid-phase pinocytosis and Fc receptor-mediated phagocytosis, but they had little effect on the receptor-mediated endocytosis of diI-labeled, acetylated, low density lipoprotein. Large solute probes of endocytosis reported greater inhibition by wortmannin than smaller probes did, indicating that macropinocytosis was affected more than micropinocytosis. Since macropinocytosis and phagocytosis are actin-mediated processes, we expected that their inhibition by wortmannin resulted from deficient signaling from macrophage colony-stimulating factor (M-CSF) receptors or Fc receptors to the actin cytoskeleton. However, video microscopy showed cell surface ruffling in wortmannin-treated cells, and increased ruffling after addition of M-CSF or phorbol myristate acetate. Quantitative measurements of video data reported slightly diminished ruffling in wortmannin-treated cells. Remarkably, the ruffles that formed in wortmannin-treated macrophages all receded into the cytoplasm without closing into macropinosomes. Similarly, wortmannin and LY294002 did not inhibit the extension of actin-rich pseudopodia along IgG-opsonized sheep erythrocytes, but instead prevented them from closing into phagosomes. These findings indicate that PI 3-kinase is not necessary for receptor-mediated stimulation of pseudopod extension, but rather functions in the closure of macropinosomes and phagosomes into intracellular organelles.
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“Hence, consumption of 4,5-PIP2 by PI3K must contribute to the dissociation of PLCδ-PH-GFP.”
From Localized Biphasic Changes in Phosphatidylinositol-4,5-Bisphosphate at Sites of Phagocytosis (2000) · cites this paper as Araki et al. 1996
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“This kinase appears to be essential for phagocytosis since inhibitors such as wortmannin impair particle engulfment (Ninomiya et al. 1994; Araki et al. 1996; Cox et al. 1999).”
From Localized Biphasic Changes in Phosphatidylinositol-4,5-Bisphosphate at Sites of Phagocytosis (2000) · cites this paper as Araki et al. 1996
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“The increase in 3,4,5-PIP3 predicted to occur during phagocytosis, based on the reported activation of PI3K (Araki et al. 1996; Cox et al. 1999), did not affect the distribution of PLCδ-PH-GFP.”
From Localized Biphasic Changes in Phosphatidylinositol-4,5-Bisphosphate at Sites of Phagocytosis (2000) · cites this paper as Araki et al. 1996
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“While wortmannin-treated cells fail to internalize particles, they nevertheless display marked actin reassembly under the adherent RBCs (Araki et al. 1996; Cox et al. 1999; and our own observations, not shown).”
From Localized Biphasic Changes in Phosphatidylinositol-4,5-Bisphosphate at Sites of Phagocytosis (2000) · cites this paper as Araki et al. 1996
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Vlahos, C. J., Matter, W. F., Hui, K. Y., & Brown, R. F. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37680-9 · Cited by 3,248 · cited 3×
“Its inhibitory effects are reversible, and it is specific for PI 3-kinase (35).”
BackgroundResultOncogenes and signal transduction
Cantley, L. C., Auger, K. R., Carpenter, C. F., Duckworth, B. C., Graziani, A., Kapeller, R., & Soltoff, S. P. (1991) · Cell · doi:10.1016/0092-8674(91)90639-g · Cited by 2,697 · cited 1×
“Nonetheless, a number of cellular processes require PI 3-kinase activity, including mitogenesis (6), membrane ruffling (18, 36), fluid-phase pinocytosis (3, 8), the respiratory burst (2, 22), and lysosomal enzyme sorting (5, 10, 25).”
BackgroundGoldstein, J. L., Ho, Y. K., Basu, S. K., & Brown, M. S. (1979) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.76.1.333 · Cited by 2,447 · cited 1×
“To confirm that the observed uptake of diI-acLDL was receptor mediated, labeling and endocytosis of diI-acLDL were measured in the presence and absence of excess mBSA, which competitively binds the scavenger receptor (13, 17).”
BackgroundArcaro, A., & Wymann, M. P. (1993) · Biochemical Journal · doi:10.1042/bj2960297 · Cited by 1,138 · cited 1×
“Wortmannin inhibits agonist-induced responses but not phorbol ester-induced responses in neutrophils (1, 2), indicating that PI 3-kinase functions upstream of protein kinase C in that signaling cascade.”
BackgroundType I macrophage scavenger receptor contains α-helical and collagen-like coiled coils
Kodama, T., Freeman, M. W., Rohrer, L., Zabrecky, J. R., Matsudaira, P. T., & Krieger, M. (1990) · Nature · doi:10.1038/343531a0 · Cited by 1,036
Phosphatidylinositol 3-Kinase Encoded by Yeast VPS 34 Gene Essential for Protein Sorting
Schu, P. V., Takegawa, K., Fry, M. J., Stack, J. H., Waterfield, M. D., & Emr, S. D. (1993) · Science · doi:10.1126/science.8385367 · Cited by 778 · cited 1×
“Nonetheless, a number of cellular processes require PI 3-kinase activity, including mitogenesis (6), membrane ruffling (18, 36), fluid-phase pinocytosis (3, 8), the respiratory burst (2, 22), and lysosomal enzyme sorting (5, 10, 25).”
BackgroundSwanson, J. A., & Watts, C. K. W. (1995) · Trends in Cell Biology · doi:10.1016/s0962-8924(00)89101-1 · Cited by 771
Self-citationYano, H., Nakanishi, S., Kimura, K. D., Hanai, N., Saitoh, Y., Fukui, Y., Nonomura, Y., & Matsuda, Y. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)74466-4 · Cited by 725
Phosphoinositides as Regulators in Membrane Traffic
Camilli, P. V. D., Emr, S. D., McPherson, P. S., & Novick, P. (1996) · Science · doi:10.1126/science.271.5255.1533 · Cited by 706 · cited 1×
“It phosphorylates phosphoinositides at the D3 hydroxyl of inositol, producing phosphatidylinositol 3-phosphate, phosphatidylinositol (3, 4)-bisphosphate, or phosphatidylinositol (3, 4, 5)-trisphosphate (11).”
BackgroundMutations in human dynamin block an intermediate stage in coated vesicle formation
van der Bliek, A., Redelmeier, T., Damke, H., Tisdale, E. J., Meyerowitz, E. M., & Schmid, S. (1993) · The Journal of Cell Biology · doi:10.1083/jcb.122.3.553 · Cited by 698 · cited 1×
“tein implicated in elathrin-mediated endocytosis (14, 34).”
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Huth, U., Schubert, R., & Peschka‐Süss, R. (2006) · Journal of Controlled Release · doi:10.1016/j.jconrel.2005.10.018 · Cited by 222
Myosin X is a downstream effector of PI(3)K during phagocytosis
Cox, D., Berg, J. S., Cammer, M., Chinegwundoh, J. O., Dale, B. M., Cheney, R. E., & Greenberg, S. (2002) · Nature Cell Biology · doi:10.1038/ncb805 · Cited by 218
“The phenotype observed by expression of Myo10 tail (that is, inhibition of phagocytosis without an effect on actin assembly) was similar to the phenotype seen after inhibition of PI(3)”
ResultMyosin-X, a novel myosin with pleckstrin homology domains, associates with regions of dynamic actin
Berg, J. S., Derfler, B. H., Pennisi, C., Corey, D. P., & Cheney, R. E. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.19.3439 · Cited by 218
Membrane Traffic Exploited by Protein Toxins
Sandvig, K., & van Deurs, B. (2002) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.18.011502.142107 · Cited by 218
Chiu, Y.-L., Ho, Y., Chen, Y., Peng, S., Ke, C., Chen, K., Mi, F., & Sung, H. (2010) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.05.023 · Cited by 216
Surface Functionality of Nanoparticles Determines Cellular Uptake Mechanisms in Mammalian Cells
Saha, K., Kim, S. T., Yan, B., Miranda, O. R., Alfonso, F. S., Shlosman, D., & Rotello, V. M. (2012) · Small · doi:10.1002/smll.201201129 · Cited by 214
Schlam, D., Bagshaw, R. D., Freeman, S. A., Collins, R. F., Pawson, T. J., Fairn, G. D., & Grinstein, S. (2015) · Nature Communications · doi:10.1038/ncomms9623 · Cited by 222
“Thus, fission of small phagosomes is followed by PtdIns(4,5)P2 catabolism31, and consequently actin disassembly.”
BackgroundMethodInfluentialGulping rather than sipping: macropinocytosis as a way of virus entry
Mercer, J., & Helenius, A. (2012) · Current Opinion in Microbiology · doi:10.1016/j.mib.2012.05.016 · Cited by 210
“PI(3) kinase has been implicated in several stages of macropinocytosis, from membrane protrusion, to macropinosome trafficking and fusion [18,57–62].”
BackgroundHama, S., Akita, H., Ito, R., Mizuguchi, H., Hayakawa, T., & Harashima, H. (2005) · Molecular Therapy · doi:10.1016/j.ymthe.2005.10.007 · Cited by 213
“Concerning the kint value, it has recently been reported that Ad enters, not only via clathrin-mediated endocytosis [16,17], but also via macropinocytosis [18,19], which is actively driven by signal transduction after the binding of the RGD motif to the integrin receptor for cellular entry [20–22].”
BackgroundGene Electrotransfer: A Mechanistic Perspective
Rosazza, C., Meglič, S. H., Zumbusch, A., Rols, M., & Miklavčič, D. (2016) · Current Gene Therapy · doi:10.2174/1566523216666160331130040 · Cited by 228
Histone Deacetylase 6 Regulates Growth Factor-Induced Actin Remodeling and Endocytosis
Gao, Y., Hubbert, C. C., Lu, J., Lee, Y.-S., Lee, J., & Yao, T. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00393-07 · Cited by 209
“4B), which prevents macropinosome formation (2, 4, 8).”
BackgroundMidoux, P., Breuzard, G., Gomez, J., & Pichon, C. (2008) · Current Gene Therapy · doi:10.2174/156652308786071014 · Cited by 225
Hirosue, S., Vokali, E., Raghavan, V. R., Rincón-Restrepo, M., Lund, A. W., Corthésy-Henrioud, P., Capotosti, F., Halin, C., Hugues, S., & Swartz, M. A. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1302492 · Cited by 200
Phosphoinositide 3-kinase in immunological systems
Fruman, D. A., & Cantley, L. C. (2002) · Seminars in Immunology · doi:10.1006/smim.2001.0337 · Cited by 208
Kim, S. M., Nguyen, T. T., Ravi, A., Kubiniok, P., Finicle, B. T., Jayashankar, V., Malacrida, L., Hou, J., Robertson, J., Gao, D., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-1215 · Cited by 199
“PIP3 produced by type I PI3Ks is required for macropinosome closure; in some cell types, PIP3 is also required for membrane ruffling (12, 13).”
BackgroundSphingomyelinase Treatment Induces ATP-independent Endocytosis
Zha, X., Pierini, L. M., Leopold, P. L., Skiba, P. J., Tabas, I. A., & Maxfield, F. R. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.140.1.39 · Cited by 201
“Inhibition of PI3 kinase by wortmannin and LY294002 was reported to prevent invaginated phagosomes from closure on the plasma membrane (Araki et al., 1996).”
Macropinocytosis confers resistance to therapies targeting cancer anabolism
Jayashankar, V., & Edinger, A. L. (2020) · Nature Communications · doi:10.1038/s41467-020-14928-3 · Cited by 200
Coppolino, M. G., Krause, M., Hagendorff, P., Monner, D. A., Trimble, W. S., Grinstein, S., Wehland, J., & Sechi, A. S. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.23.4307 · Cited by 200
Porphyromonas gingivalis Traffics to Autophagosomes in Human Coronary Artery Endothelial Cells
Dorn, B. R., Dunn, W. A., & Progulske‐Fox, A. (2001) · Infection and Immunity · doi:10.1128/iai.69.9.5698-5708.2001 · Cited by 200
“have also demonstrated that the phosphoinositide 3-kinase (PI3-kinase) targeted by these drugs is not required for endocytosis (1, 49).”
BackgroundNiedergang, F., Colucci‐Guyon, E., Dubois, T., Raposo, G., & Chavrier, P. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200210069 · Cited by 198
“Inhibition of phosphatidylinositol 3-kinase (PI3K) was shown to block phago- cytosis (Araki et al., 1996; Cox et al., 1999; unpublished data).”
BackgroundWhat transgenic mice tell us about neurodegenerative disease
Gurney, M. E. (2000) · BioEssays · doi:10.1002/(sici)1521-1878(200003)22:3 · Cited by 38
Mechanism of Cellular Uptake of Highly Fluorescent Conjugated Polymer Nanoparticles
Fernando, L. P., Kandel, P. K., Yu, J., McNeill, J., Ackroyd, P. C., & Christensen, K. (2010) · Biomacromolecules · doi:10.1021/bm1007103 · Cited by 196
Antimicrobial Mechanisms of Macrophages and the Immune Evasion Strategies of Staphylococcus aureus
Flannagan, R. S., Heit, B., & Heinrichs, D. E. (2015) · Pathogens · doi:10.3390/pathogens4040826 · Cited by 211
“5 μm) into a membrane bound vacuole termed the phagosome [19–21].”
BackgroundRen, Y., Zheng, G., You, L., Wen, L., Li, C., Fu, X., & Zhou, L. M. (2017) · Journal of Functional Foods · doi:10.1016/j.jff.2017.03.062 · Cited by 194
Uses and abuses of macropinocytosis
Bloomfield, G., & Kay, R. R. (2016) · Journal of Cell Science · doi:10.1242/jcs.176149 · Cited by 193
“When PIP3 production is attenuated either with drugs or genetically, macropinocytosis is inhibited to striking extents (Araki et al., 2007, 1996; Buczynski et al., 1997; Hoeller et al., 2013; Zhou et al., 1998).”
BackgroundAraki, N., Hatae, T., Furukawa, A., & Swanson, J. A. (2002) · Journal of Cell Science · doi:10.1242/jcs.00235 · Cited by 190
“Like FcRmediated phagocytosis, macropinocytosis involves Rac1, Cdc42 and Arf6 (Radhakrishna et al., 1996; Zhang et al., 1999; Nobes and Marsh, 2000; West et al., 2000), and the closure of cup-shaped circular ruffles into macropinosomes requires PI3K activity (Araki et al., 1996).”
BackgroundMethodResultInfluentialSelf-citationIntegrins Form an Expanding Diffusional Barrier that Coordinates Phagocytosis
Freeman, S. A., Goyette, J., Furuya, W., Woods, E. C., Bertozzi, C. R., Bergmeier, W., Hinz, B., van der Merwe, P. A., Das, R., & Grinstein, S. (2016) · Cell · doi:10.1016/j.cell.2015.11.048 · Cited by 192
“Thus, expansion of the phagocytic cup and clearance of actin at its base – which is required for successful engulfment of large targets (Araki et al., 1996; Cox et al., 1999)– needs engagement of integrins activated by the receptors.”
Seib, F. P., Jones, A. T., & Duncan, R. (2006) · Journal of Controlled Release · doi:10.1016/j.jconrel.2006.10.020 · Cited by 190
Cell Biology of Canonical Wnt Signaling
Albrecht, L. V., Tejeda‐Muñoz, N., & Robertis, E. M. D. (2021) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-120319-023657 · Cited by 197
Molecular aspects of the endocytic pathway
Clague, M. J. (1998) · Biochemical Journal · doi:10.1042/bj3360271 · Cited by 189
Phosphatidylserine receptors: Enhancers of enveloped virus entry and infection
Møller-Tank, S., & Maury, W. J. (2014) · Virology · doi:10.1016/j.virol.2014.09.009 · Cited by 192
“Both require phosphoinositide 3-kinase (PI3K) signaling (Araki et al., 1996) , phospholipase Cγ (Amyere et al., 2000; Cheeseman et al., 2006) , Rac1 (Caron and Hall, 1998; Ridley et al., 1992) , and dynamin (Liu et al., 2008; Cao et al., 2007; Gold et al., 1999; Tse et al., 2003) , making differentiation between the t…”
Role of Phosphoinositide 3-Kinase in Innate Immunity
Hazeki, K., Nigorikawa, K., & Hazeki, O. (2007) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.30.1617 · Cited by 191
Veldhoen, S., Laufer, S. D., Trampe, A., & Restle, T. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl941 · Cited by 191
“First we analysed the effect of wortmannin, a compound, which is supposed to affect clathrin-dependent endocytosis (85) and macropinocytosis (86).”
Macropinocytosis in Different Cell Types: Similarities and Differences
Lin, X. P., Mintern, J. D., & Gleeson, P. A. (2020) · Membranes · doi:10.3390/membranes10080177 · Cited by 185
“Peripheral and dorsal ruffles still form in wortmannin-treated BMDMs but do not close to form macropinosomes; rather, they recede back into the cytoplasm, showing that PI3K is required for macropinosome closure [19].”
BackgroundInfluentialVarin, A., Mukhopadhyay, S., Herbein, G., & Gordon, S. (2009) · Blood · doi:10.1182/blood-2009-08-236711 · Cited by 194
The Evolving Field of Human Papillomavirus Receptor Research: a Review of Binding and Entry
Raff, A. B., Woodham, A. W., Raff, L. M., Skeate, J. G., Yan, L., Silva, D. M. D., Schelhaas, M., & Kast, W. M. (2013) · Journal of Virology · doi:10.1128/jvi.00330-13 · Cited by 181
Bulk Membrane Retrieval in the Synaptic Terminal of Retinal Bipolar Cells
Holt, M. G., Cooke, A., Wu, M. M., & Lagnado, L. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-04-01329.2003 · Cited by 183
“Bulk membrane retrieval was dependent on the activity of PI 3-kinase In macrophages and cell lines, bulk membrane retrieval is dependent on the activity of PI 3-kinase, an enzyme that has also been implicated in vesicular membrane traffic (Clague et al., 1995; Araki et al., 1996).”
BackgroundInfluentialLipid signaling and the modulation of surface charge during phagocytosis
Yeung, T., & Grinstein, S. (2007) · Immunological Reviews · doi:10.1111/j.1600-065x.2007.00546.x · Cited by 182
“Interestingly, inhibitors such as wortmannin or LY294002 inhibited only the internalization of large particles ( 3 mm in diameter) but affected smaller particles minimally (120, 121).”
BackgroundAfrican Swine Fever Virus Uses Macropinocytosis to Enter Host Cells
Sánchez, E. G., Quintas, A., Pérez-Núñez, D., Nogal, M., Barroso, S., Carrascosa, Á. L., & Revilla, Y. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002754 · Cited by 180
Duclos, S., Diez, R., Garin, J., Papadopoulou, B., Descoteaux, A., Stenmark, H., & Desjardins, M. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.19.3531 · Cited by 175
Hofmann, H., Li, X., Zhang, X., Liu, W. Y., Krämer-Kühl, A., Kaup, F. ‐., Soldan, S. S., González‐Scarano, F., Weber, F., He, Y., et al. (2013) · Journal of Virology · doi:10.1128/jvi.02628-12 · Cited by 178
“In order to investigate if macropinocytosis is also involved in SFTSV Gn/Gc-driven entry, we pretreated target cells with wortmannin, a covalent inhibitor of the macropinocytosis regulator phosphoinositide 3-kinase (51), prior to infection with pseudotypes (Fig.”
MethodSyk and pTyr’d: Signaling through the B cell antigen receptor
Geahlen, R. (2009) · Biochimica et Biophysica Acta · doi:10.1016/j.bbamcr.2009.03.004 · Cited by 183
EGFR-Pak signaling selectively regulates glutamine deprivation-induced macropinocytosis
Lee, S.-W., Zhang, Y., Jung, M., Cruz, N., Alas, B., & Commisso, C. (2019) · Developmental Cell · doi:10.1016/j.devcel.2019.05.043 · Cited by 172
“PI3K signaling plays a well-documented role in macropinosome formation (Araki et al., 1996; Swanson, 2008; Yoshida et al., 2018) and in line with previous reports, PI3K inhibition blocked inducible macropinocytosis (Figures S4J–S4N).”
ResultKanazawa, H., Ohsawa, K., Sasaki, Y., Kohsaka, S., & Imai, Y. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109218200 · Cited by 174
The Role of Neutrophils and Monocytes in Innate Immunity
Kantari‐Mimoun, C., Pederzoli-Ribeil, M., & Witko‐Sarsat, V. (2008) · KARGER eBooks · doi:10.1159/000136335 · Cited by 177
Sequential signaling in plasma-membrane domains during macropinosome formation in macrophages
Yoshida, S., Hoppe, A. D., Araki, N., & Swanson, J. A. (2009) · Journal of Cell Science · doi:10.1242/jcs.053207 · Cited by 168
“…to macropinosomes in human epidermoid carcinoma cells (Araki et al., 2006; Araki et al., 2007) and that PI3K-inhibitortreated macrophages make circular ruffles that recede without closing into macropinosomes (i.e. ruffle closure without cup closure) (Araki et al., 1996; Araki et al., 2003).”
BackgroundResultInfluentialSelf-citationInhibitory ITAMs as novel regulators of immunity
Blank, U., Launay, P., Benhamou, M., & Monteiro, R. C. (2009) · Immunological Reviews · doi:10.1111/j.1600-065x.2009.00832.x · Cited by 175
“Indeed, PI3K phosphorylation is known to enhance phagocytosis (91) and to downregulate MAPK and nuclear factor-jB (NF-jB) activity necessary for TNFa production (46, 92).”
BackgroundA plasma membrane template for macropinocytic cups
Veltman, D. M., Williams, T. D., Bloomfield, G., Chen, B., Betzig, E., Insall, R. H., & Kay, R. R. (2016) · eLife · doi:10.7554/elife.20085 · Cited by 164
Peng, S., Tseng, M. T., Ho, Y., Wei, M.-C., Liao, Z.-X., & Sung, H. (2010) · Biomaterials · doi:10.1016/j.biomaterials.2010.08.081 · Cited by 168
MYC Mediates Large Oncosome-Induced Fibroblast Reprogramming in Prostate Cancer
Minciacchi, V. R., Spinelli, C., Reis-Sobreiro, M., Cavallini, L., You, S., Zandian, M., Li, X., Mishra, R., Chiarugi, P., Adam, R. M., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-16-2942 · Cited by 168
“The PI3K inhibitor, Wortmannin (WTN), and the actin polymerization inhibitor, cytochalasin-D (CYT-D) (27,28), typically used to block both phagocytosis and macropinocytosis (29), significantly perturbed LO uptake (Supplementary Fig.”
BackgroundHiltbold, E. M., Vlad, A., Ciborowski, P. S., Watkins, S. C., & Finn, O. J. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.7.3730 · Cited by 167
Requirement for Rho GTPases and PI 3-kinases during apoptotic cell phagocytosis by macrophages
Leverrier, Y., & Ridley, A. J. (2001) · Current Biology · doi:10.1016/s0960-9822(01)00047-1 · Cited by 164
Size of IgG-Opsonized Particles Determines Macrophage Response during Internalization
Koval, M. H., Preiter, K., Adles, C., Stahl, P. D., & Steinberg, T. H. (1998) · Experimental Cell Research · doi:10.1006/excr.1998.4110 · Cited by 161
Novel PI 3-kinase-dependent mechanisms of trypanosome invasion and vacuole maturation
Woolsey, A. M., Sunwoo, L., Petersen, C. A., Brachmann, S. M., Cantley, L. C., & Burleigh, B. A. (2003) · Journal of Cell Science · doi:10.1242/jcs.00666 · Cited by 160
“…along the endocytic pathway (Li et al., 1995; Kjeken et al., 2001), insulin-stimulated exocytosis (Watson and Pessin, 2001), phagocytic events (Araki et al., 1996; Cox et al., 1999; Marshall et al., 2001; Vieira et al., 2001; Fratti et al., 2001) and actin remodeling (Greenwood et al., 1998;…”
BackgroundPhosphoinositides in endocytosis
Posor, Y., Eichhorn‐Grünig, M., & Haucke, V. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2014.09.014 · Cited by 176
Drinking a lot is good for dendritic cells
Norbury, C. C. (2006) · Immunology · doi:10.1111/j.1365-2567.2006.02335.x · Cited by 160
Vaid, A., Ranjan, R., Smythe, W. A., Hoppe, H. C., & Sharma, P. (2010) · Blood · doi:10.1182/blood-2009-08-238972 · Cited by 157
Zsengellér, Z. K., Otake, K., Hossain, S.-A., Berclaz, P., & Trapnell, B. C. (2000) · Journal of Virology · doi:10.1128/jvi.74.20.9655-9667.2000 · Cited by 156
“As expected, wortmannin, a specific blocker of phosphatidylinositol 3-OH kinase (PI3K) (46), phagocytosis (3), and adenovirus internalization (30), did not block virion attachment to the cell surface (panels G and H), but virions were poorly internalized and did not localize as large extranuclear aggregations of fluor…”
BackgroundMontaner, L. J., Silva, R. P. D., Sun, J., Sutterwala, S. S., Hollinshead, M. S., Vaux, D. J., & Gordon, S. (1999) · PubMed · Cited by 155
The origins and evolution of macropinocytosis
King, J., & Kay, R. R. (2018) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2018.0158 · Cited by 152
Meier, O. C., & Greber, U. F. (2003) · The Journal of Gene Medicine · doi:10.1002/jgm.409 · Cited by 160
“PI3K acts downstream of receptor tyrosine kinases and of tether/stimulating receptors, such as αv integrins, and it is required for the completion of ruffles and the formation of macropinosomes [112,120].”
Backgroundv-SNARE-dependent secretion is required for phagocytosis
Hackam, D. J., Rotstein, O. D., Sjölin, C., Schreiber, A. D., Trimble, W. S., & Grinstein, S. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.20.11691 · Cited by 153
Membrane recruitment of Rac1 triggers phagocytosis
Castellano, F., Montcourrier, P., & Chavrier, P. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.17.2955 · Cited by 153
Phagocytosis by the Retinal Pigment Epithelium: Recognition, Resolution, Recycling
Kwon, W., & Freeman, S. A. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.604205 · Cited by 205
Gonçalves, C., Mennesson, E., Fuchs, R., Gorvel, J., Midoux, P., & Pichon, C. (2004) · Molecular Therapy · doi:10.1016/j.ymthe.2004.05.023 · Cited by 151
Canton, J., Schlam, D., Breuer, C., Gütschow, M., Glogauer, M., & Grinstein, S. (2016) · Nature Communications · doi:10.1038/ncomms11284 · Cited by 148
Dynamics of Cytoskeletal Proteins during Fcγ Receptor-mediated Phagocytosis in Macrophages
Diakonova, M., Bokoch, G., & Swanson, J. A. (2002) · Molecular Biology of the Cell · doi:10.1091/mbc.01-05-0273 · Cited by 151
“However, although wortmannin does not inhibit cell surface ruffling ( Araki et al., 1996 ), it did inhibit the M-CSF–induced increases in macrophage F-actin (Figure 4C).”
BackgroundMethodResultInfluentialSelf-citationPhosphoinositides in phagocytosis and macropinocytosis
Levin‐Konigsberg, R., Grinstein, S., & Schlam, D. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2014.09.005 · Cited by 151
Sasso, M. S., Lollo, G., Pitorre, M., Solito, S., Pinton, L., Valpione, S., Bastiat, G., Mandruzzato, S., Bronte, V., Marigo, I., et al. (2016) · Biomaterials · doi:10.1016/j.biomaterials.2016.04.010 · Cited by 150
Bohdanowicz, M., Balkin, D. M., Camilli, P. V. D., & Grinstein, S. (2011) · Molecular Biology of the Cell · doi:10.1091/mbc.e11-06-0489 · Cited by 152
“Disassembly of the actin scaffold is required for completion of particle internalization (Araki et al., 1996; Scott et al., 2005).”
BackgroundGeng, J., Li, K., Ding, D., Zhang, X., Qin, W., Liu, J., Tang, B. Z., & Liu, B. (2012) · Small · doi:10.1002/smll.201200814 · Cited by 146
Physical Constraints and Forces Involved in Phagocytosis
Jaumouillé, V., & Waterman, C. M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01097 · Cited by 156
“pathway(s) orchestrating these events are incompletely understood, it is known to involve the phosphoinositide 3 kinase (PI3K), which is required for internalization of particle larger than 3μm (8, 192, 196).”
BackgroundEgami, Y., Taguchi, T., Maekawa, M., Arai, H., & Araki, N. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00374 · Cited by 145
“Although PDGF-induced membrane ruffling in fibroblasts is eliminated by PI3K inhibitors, membrane ruffling and circular ruffle formation in macrophages and EGF-stimulated A431 cells are resistant to these inhibitors (Araki et al., 1996, 2006, 2007).”
BackgroundSelf-citationCoppolino, M. G., Dierckman, R., Loijens, J. C., Collins, R. F., Pouladi, M. A., Jongstra‐Bilen, J., Schreiber, A. D., Trimble, W. S., Anderson, R. A., & Grinstein, S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m209046200 · Cited by 142
Tilton, B., Andjelković, M., Didichenko, S. A., Hemmings, B. A., & Thelen, M. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.44.28096 · Cited by 143
Stimulated endocytosis in penetratin uptake: Effect of arginine and lysine
Åmand, H. L., Fant, K., Nordén, B., & Esbjörner, E. K. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.04.039 · Cited by 146
Lin, H., Singla, B., Ghoshal, P., Faulkner, J., Cherian‐Shaw, M., O'Connor, P. M., She, J., de Chantemèle, E. J. B., & Csányi, G. (2018) · British Journal of Pharmacology · doi:10.1111/bph.14429 · Cited by 144
“, 2011), (ii) PI3K blockers (Araki et al., 1996) and (iii) inhibitors of sodium/ hydrogen exchangers (NHEs) (Koivusalo et al.”
BackgroundLeukotriene B 4 Augments Neutrophil Phagocytosis of Klebsiella pneumoniae
Mancuso, P., Nana-Sinkam, P. S., & Peters-Golden, M. L. (2001) · Infection and Immunity · doi:10.1128/iai.69.4.2011-2016.2001 · Cited by 141
“cals) and C3bi (Sigma) as described previously (1, 29).”
da Silva, F. P., Aloulou, M., Skurnik, D., Benhamou, M., Andremont, A., Velasco, I. T., Chiamolera, M., Verbeek, J. S., Launay, P., & Monteiro, R. C. (2007) · Nature Medicine · doi:10.1038/nm1665 · Cited by 139
Suh, C.-I., Stull, N. D., Li, X. J., Tian, W., Price, M. O., Grinstein, S., Yaffe, M. B., Atkinson, S. J., & Dinauer, M. C. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20052085 · Cited by 145
Celli, J., Olivier, M., & Finlay, B. B. (2001) · The EMBO Journal · doi:10.1093/emboj/20.6.1245 · Cited by 141
Modular components of phagocytosis
Greenberg, S. (1999) · Journal of Leukocyte Biology · doi:10.1002/jlb.66.5.712 · Cited by 137
“Furthermore, inhibition of PI 3-kinase was not associated with quantitative differences in FcgR-mediated actin assembly [75], confirming earlier qualitative assessments of F-actin in PI 3-kinase-inhibited macrophages challenged with IgG-coated particles [28, 76].”
ResultKawaguchi, Y., Takeuchi, T., Kuwata, K., Chiba, J., Hatanaka, Y., Nakase, I., & Futaki, S. (2016) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.6b00082 · Cited by 145
Drinking problems: mechanisms of macropinosome formation and maturation
Buckley, C. M. F., & King, J. (2017) · FEBS Journal · doi:10.1111/febs.14115 · Cited by 140
“The role of PI(3,4,5)P3 appears to be complex; whilst in PDGF-stimulated PAE cells it appears to be required for ruffle formation [39], others report a much later role during cup closure in both EGF-stimulated A431 cells and M-CSF-stimulated BMDMs [38, 40].”
BackgroundFujii, M., Kawai, K., Egami, Y., & Araki, N. (2013) · Scientific Reports · doi:10.1038/srep02385 · Cited by 137
Self-citationMechanisms of Fc Receptor and Dectin‐1 Activation for Phagocytosis
Goodridge, H. S., Underhill, D. M., & Touret, N. (2012) · Traffic · doi:10.1111/j.1600-0854.2012.01382.x · Cited by 147
“Pharmacological inhibition of PI 3-kinase blocks phagocytosis of large (≥3 μm) IgG-opsonized particles and zymosan (58,59).”
BackgroundSignaling by epithelial members of the CEACAM family – mucosal docking sites for pathogenic bacteria
Tchoupa, A. K., Schuhmacher, T., & Hauck, C. R. (2014) · Cell Communication and Signaling · doi:10.1186/1478-811x-12-27 · Cited by 136
“In numerous endocytic processes, phosphatidylinositol phosphates (PIPs) play an important role [74,75].”
BackgroundVercauteren, D., Rejman, J., Martens, T., Demeester, J., Smedt, S. C. D., & Braeckmans, K. (2012) · Journal of Controlled Release · doi:10.1016/j.jconrel.2012.05.020 · Cited by 136
Dynamic macrophage “probing” is required for the efficient capture of phagocytic targets
Flannagan, R. S., Harrison, R. E., Yip, C. M., Jaqaman, K., & Grinstein, S. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.201007056 · Cited by 135
“…of the phagocytes can be obtained whether in the presence of cytochalasin (Newman et al., 1991), after inhibition of Rac (Cox et al., 1997; Caron and Hall, 1998), or in cells treated with tyrosine kinase inhibitors or wortmannin (Greenberg et al., 1993; Ninomiya et al., 1994; Araki et al., 1996).”
BackgroundThe Internalization and Degradation of Human Copper Transporter 1 following Cisplatin Exposure
Holzer, A. K., & Howell, S. B. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-1710 · Cited by 140
“Neutral dextran of this molecular weight enters cells via a macropinocytotic process, and the uptake of this molecule served as a control (21, 22).”
BackgroundSubversion of Phagocytosis for Pathogen Survival
Sarantis, H., & Grinstein, S. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2012.09.001 · Cited by 137
“Inhibiting PtdIns3K activity can have profound effects on phagocytosis, particularly during uptake of large particles (Araki et al., 1996; Cox et al., 1999).”
BackgroundIn vivo analysis of 3-phosphoinositide dynamics during Dictyostelium phagocytosis and chemotaxis
Dormann, D., Weijer, G., DOWLER, S., & Weijer, C. J. (2004) · Journal of Cell Science · doi:10.1242/jcs.01579 · Cited by 131
“In macrophages PI3-kinases have been shown to be essential for the cytoskeletal rearrangements during the phagocytic process and have been implicated in the process of phagosome and macropinosome closure (Araki et al., 1996; Stephens et al., 2002).”
BackgroundPagan, J. K., Wylie, F. G., Joseph, S., Widberg, C., Bryant, N. J., James, D. E., & Stow, J. L. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00006-x · Cited by 130
Tay, M. Z., Liu, P., Williams, L. D., McRaven, M. D., Sawant, S. S., Gurley, T. C., Xu, T. T., Dennison, S. M., Liao, H., Chenine, A., et al. (2016) · PLoS Pathogens · doi:10.1371/journal.ppat.1005817 · Cited by 136
“Antibody-dependent internalization processes vary depending on the target's properties [69] [70] [71] [72] [73] [74] [75] [76] .”
Sedwick, C. E., Morgan, M. M., Jusino, L., Cannon, J. L., Miller, J., & Burkhardt, J. K. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.3.1367 · Cited by 130
Neurofibromin controls macropinocytosis and phagocytosis in Dictyostelium
Bloomfield, G., Traynor, D., Sander, S. P., Veltman, D. M., Pachebat, J. A., & Kay, R. R. (2015) · eLife · doi:10.7554/elife.04940 · Cited by 126
“, 1997), allowing the spatially restricted formation of phosphatidylinositol trisphosphate (PIP3) and other inositol phospholipids that occurs during macropinocytosis (Araki et al., 1996; Buczynski et al., 1997; Hoeller et al., 2013).”
BackgroundMontaner, L. J., SILVA, R. P. D., Sun, J., Sutterwala, S. S., Hollinshead, M. S., Vaux, D. J., & Gordon, S. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.8.4606 · Cited by 130
Cox, D., Dale, B. M., Kashiwada, M., Helgason, C. D., & Greenberg, S. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.193.1.61 · Cited by 158
The Mechanism of Phagocytosis: Two Stages of Engulfment
Richards, D. M., & Endres, R. G. (2014) · Biophysical Journal · doi:10.1016/j.bpj.2014.07.070 · Cited by 126
“Finally, phosphatidylinositol 3-kinase (PI3K) has been shown to be required for phagosome contraction during the latter stages of engulfment (31).”
BackgroundViboud, G. I., & Bliska, J. B. (2001) · The EMBO Journal · doi:10.1093/emboj/20.19.5373 · Cited by 127
Metadata
- Authors
- Araki, N., Johnson, M. T., & Swanson, J. A.
- Affiliations
- Harvard University (US)
- ORCID
- Venue
- The Journal of cell biology
- Publisher
- Rockefeller University Press
- Published
- 1996-12-01
- Volume
- 135
- Issue
- 5
- Pages
- 1249-1260
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2121091
- OpenAlex
- W2104603012
- Cited by
- 949
- References
- 39
- Citations by year
- 2026: 9 · 2025: 22 · 2024: 25 · 2023: 17 · 2022: 28 · 2021: 37 · 2020: 38 · 2019: 20 · 2018: 39 · 2017: 35 · 2016: 51 · 2015: 26 · 2014: 49 · 2013: 46 · 2012: 48
- 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)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- phosphatidylinositol 3-kinase, macropinocytosis, phagocytosis, macrophages, wortmannin, LY294002, actin cytoskeleton, Fc receptors, macrophage colony-stimulating factor, pseudopod extension, micropinocytosis
- MeSH terms
- Wortmannin, Androstadienes, Animals, Cell Membrane, Cells, Cultured, Chromones, Enzyme Inhibitors, Female, Fluorescent Dyes, Lysosomes, Macrophages, Male, Mice, Inbred C3H, Morpholines, Phagocytosis, Phagosomes, Pinocytosis, Pseudopodia, Receptors, Fc, Tetradecanoylphorbol Acetate, Organelles, Macrophage Colony-Stimulating Factor, Phosphotransferases (Alcohol Group Acceptor), Phosphatidylinositol 3-Kinases, Mice
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