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Differential Role of Actin, Clathrin, and Dynamin in Fcγ Receptor-mediated Endocytosis and Phagocytosis
Open accessAbstract
Clustering of macrophage Fc gamma receptors by multimeric immunoglobulin complexes leads to their internalization. Formation of small aggregates leads to endocytosis, whereas large particulate complexes induce phagocytosis. In RAW-264.7 macrophages, Fc gamma receptor endocytosis was found to be dependent on clathrin and dynamin and insensitive to cytochalasin. Clathrin also associates with nascent phagosomes, and earlier observations suggested that it plays an essential role in phagosome formation. However, we find that phagocytosis of IgG-coated large (> or =3 microm) particles was unaffected by inhibition of dynamin or by reducing the expression of clathrin using antisense mRNA but was eliminated by cytochalasin, implying a distinct mechanism dependent on actin assembly. The uptake of smaller particles (< or =1 microm) was only partially blocked by cytochalasin. Remarkably, the cytochalasin-resistant component was also insensitive to dominant-negative dynamin I and to clathrin antisense mRNA, implying the existence of a third internalization mechanism, independent of actin, dynamin, and clathrin. The uptake of small particles occurred by a process distinct from fluid phase pinocytosis, because it was not inhibited by dominant-negative Rab5. The insensitivity of phagocytosis to dominant-negative dynamin I enabled us to test the role of dynamin in phagosomal maturation. Although internalization of receptors from the plasma membrane was virtually eliminated by the K44A and S45N mutants of dynamin I, clearance of transferrin receptors and of CD18 from maturing phagosomes was unaffected by these mutants. This implies that removal of receptors from the phagosomal membrane occurs by a mechanism that is different from the one mediating internalization of the same receptors at the plasma membrane. These results imply that, contrary to prevailing notions, normal dynamin and clathrin function is not required for phagocytosis and reveal the existence of a component of phagocytosis that is independent of actin and Rab5.
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“which would be consistent with the gene down-regulation observed here, suggesting a differential requirement for dynamin in endocytosis not phagocytosis, similarly to what has been described for macrophages [56].”
From Genome-wide transcriptional changes induced by phagocytosis or growth on bacteria in Dictyostelium (2008) · cites this paper as [56]
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Metadata
- Authors
- Tse, S. M. L., Furuya, W., Gold, E., Schreiber, A. D., Sandvig, K., Inman, R. D., & Grinstein, S.
- Affiliations
- University Health Network (CA)
- University of Toronto (CA)
- University of Washington (US)
- University of Pennsylvania (US)
- Corresponding author
- Grinstein, Sergio
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-01
- Volume
- 278
- Issue
- 5
- Pages
- 3331-3338
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2146362515
- Cited by
- 124
- References
- 45
- Citations by year
- 2026: 2 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 4 · 2020: 4 · 2019: 4 · 2018: 5 · 2017: 2 · 2016: 9 · 2015: 5 · 2014: 7 · 2013: 5 · 2012: 7
- FWCI
- 3.58
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Keywords
- Fc gamma receptor, phagocytosis, receptor internalization, clathrin, dynamin, actin, cytochalasin, phagosome maturation, immunoglobulin complexes, macrophages, pinocytosis, Rab5, transferrin receptor, CD18
- MeSH terms
- Actins, Animals, Cell Line, Cell Membrane, Clathrin, Endocytosis, Gene Expression Regulation, Immunoglobulin G, Luminescent Proteins, Macrophages, Phagocytosis, Phagosomes, RNA, Messenger, Transcription, Genetic, RNA, Antisense, Receptors, IgG, Genes, Reporter, Protein Transport, Dynamin I, Green Fluorescent Proteins, Mice
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