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Cited by 124Cellular transport and secretionPhagocytosis and Immune RegulationMonoclonal and Polyclonal Antibodies Research

Differential Role of Actin, Clathrin, and Dynamin in Fcγ Receptor-mediated Endocytosis and Phagocytosis

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Tse, Shirley M.L., Furuya, Wendy, Gold, Elizabeth, Schreiber, Alan D., Sandvig, Kirsten, Inman, Robert D., Grinstein, Sergio·2003·Journal of Biological Chemistry
DOI 10.1074/jbc.m207966200
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Abstract

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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  • The dymA mutant phenotype is consistent with the gene down-regulation observed here, suggesting a differential requirement for dynamin in endocytosis not phagocytosis, similarly to macrophages.

    “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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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
ORCID
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2003-01
Volume
278
Issue
5
Pages
3331-3338
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.m207966200
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
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
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › 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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