A role for MARCKS, the alpha isozyme of protein kinase C and myosin I in zymosan phagocytosis by macrophages.
Open accessAbstract
Myristoylated, alanine-rich C-kinase substrate (MARCKS) is a lipopolysaccharide-induced protein kinase C (PKC) substrate that has been proposed to regulate actin-membrane interactions, as well as actin structure at the membrane. We studied the distribution of MARCKS, the alpha isozyme of PKC (PKC alpha), and myosin I in lipopolysaccharide-treated peritoneal macrophages ingesting zymosan particles. MARCKS, PKC alpha, and myosin I colocalized with F-actin and talin in the cortical cytoplasm adjacent to forming phagocytic cups. After particle ingestion was completed, myosin I, F-actin, and talin were no longer enriched in the vicinity of the phagosome. By contrast, MARCKS and PKC alpha remained associated with the phagosome membrane until after acquisition of the lysosomal marker Lamp-1. Vinculin was not detected on phagosomes at any time point examined. Phagocytosis of zymosan was accompanied by rapid and sustained phosphorylation of MARCKS. Inhibitors of PKC reduced zymosan binding to the macrophage surface and blocked the focal accumulation of F-actin, talin, phosphotyrosine-containing proteins, MARCKS, and PKC alpha beneath attached particles. We propose that PKC-dependent phosphorylation is an early signal required for zymosan phagocytosis and that MARCKS and PKC alpha have a role in phagosome maturation. The colocalization of F-actin and MARCKS at the cytoplasmic face of the nascent phagosome reinforces the hypothesis that MARCKS regulates actin structure at the membrane. Our data also suggest that myosin I functions as a mechanical motor during particle uptake.
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Both PKCα and PKCδ copurify with isolated phagosomal membranes, and some inhibitors of PKC activity have been reported to interfere with phagocytosis.
“both PKCα and PKCδ copurify with isolated phagosomal membranes (Allen and Aderem 1995; Brumell et al. 1999) and some inhibitors of PKC activity have been reported to interfere with phagocytosis (Zheleznyak and Brown 1992; Karimi et al. 1999).”
From Localized Biphasic Changes in Phosphatidylinositol-4,5-Bisphosphate at Sites of Phagocytosis (2000) · cites this paper as Allen and Aderem 1995
The Discussion reports that PKCα associates with forming phagosomes and remains on maturing phagosomes. It does not report PKCδ or show that both isoforms copurify with isolated phagosomal membranes. The separate claim about PKC inhibitors is cited to other papers in the citing sentence, so it is not assessed against Allen and Aderem. (LLM, conf=0.85)
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Cites
Greenberg, S., Chang, P., & Silverstein, S. C. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)41945-4 · Cited by 237 · see citing works
Greenberg, S., el Khoury, J., di Virgilio, F., Kaplan, E. M., & Silverstein, S. C. (1991) · The Journal of cell biology · doi:10.1083/jcb.113.4.757 · Cited by 171 · see citing works
Zheleznyak, A., & Brown, E. J. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)49803-7 · Cited by 118 · see citing works
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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
Self-citationPhagocytosis and the actin cytoskeleton
May, R. C., & Machesky, L. M. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.6.1061 · Cited by 715 · see citing works
Localized Biphasic Changes in Phosphatidylinositol-4,5-Bisphosphate at Sites of Phagocytosis
Botelho, R. J., Teruel, M., Dierckman, R., Anderson, R., Wells, A., York, J. D., Meyer, T., & Grinstein, S. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.151.7.1353 · Cited by 539 · see citing works
“In agreement with this postulate, both PKCa and PKCd copurify with isolated phagosomal membranes ( Allen and Aderem, 1995; Brumell et al., 1999) and some inhibitors of PKC activity have been reported to interfere with phagocytosis (Zheleznyak and Brown, 1992; Karimi et al., 1999).”
BackgroundPhagocytosis 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
Creatine kinase-mediated ATP supply fuels actin-based events in phagocytosis
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Johnston, D. G. W., Kearney, J., Zasłona, Z., Williams, M. A., O'Neill, L. A. J., & Corr, S. C. (2017) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2017.00201 · Cited by 44 · see citing works
- Authors
- Allen, L. H., & Aderem, A.
- Affiliations
- Laboratory of Signal Transduction, Rockefeller University, New York 10021, USA.
- Rockefeller University (US)
- ORCID
- Aderem, A
- Venue
- The Journal of experimental medicine
- Publisher
- Rockefeller University Press
- Published
- 1995-09-01
- Volume
- 182
- Issue
- 3
- Pages
- 829-840
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2192156
- OpenAlex
- W2126712915
- Cited by
- 296
- References
- 3
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 5 · 2019: 7 · 2018: 2 · 2017: 4 · 2016: 4 · 2015: 3 · 2014: 8 · 2013: 9 · 2012: 4
- FWCI
- 7.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- National Institutes of Health (1f32ai008618-01)
- National Institute of Allergy and Infectious Diseases (AI25032, AI08618)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- MARCKS, protein kinase C alpha, myosin I, zymosan phagocytosis, macrophages, phagosome maturation, F-actin, talin, MARCKS phosphorylation, lipopolysaccharide, phagocytic cup, actin-membrane interaction
- MeSH terms
- Myristoylated Alanine-Rich C Kinase Substrate, Actins, Intracellular Membranes, Isoenzymes, Lipopolysaccharides, Membrane Proteins, Models, Biological, Myosins, Phagocytosis, Phagosomes, Phosphorylation, Protein Kinase C, Protein Processing, Post-Translational, Proteins, Zymosan, Vinculin, Talin, Macrophages, Peritoneal, Macromolecular Substances, Intracellular Signaling Peptides and Proteins, Protein Kinase C-alpha
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