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PMID:17151602

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Citation

Stuart, LM, Boulais, J, Charriere, GM, Hennessy, EJ, Brunet, S, Jutras, I, Goyette, G, Rondeau, C, Letarte, S, Huang, H, Ye, P, Morales, F, Kocks, C, Bader, JS, Desjardins, M and Ezekowitz, RA (2007) A systems biology analysis of the Drosophila phagosome. Nature 445:95-101

Abstract

Phagocytes have a critical function in remodelling tissues during embryogenesis and thereafter are central effectors of immune defence. During phagocytosis, particles are internalized into 'phagosomes', organelles from which immune processes such as microbial destruction and antigen presentation are initiated. Certain pathogens have evolved mechanisms to evade the immune system and persist undetected within phagocytes, and it is therefore evident that a detailed knowledge of this process is essential to an understanding of many aspects of innate and adaptive immunity. However, despite the crucial role of phagosomes in immunity, their components and organization are not fully defined. Here we present a systems biology analysis of phagosomes isolated from cells derived from the genetically tractable model organism Drosophila melanogaster and address the complex dynamic interactions between proteins within this organelle and their involvement in particle engulfment. Proteomic analysis identified 617 proteins potentially associated with Drosophila phagosomes; these were organized by protein-protein interactions to generate the 'phagosome interactome', a detailed protein-protein interaction network of this subcellular compartment. These networks predicted both the architecture of the phagosome and putative biomodules. The contribution of each protein and complex to bacterial internalization was tested by RNA-mediated interference and identified known components of the phagocytic machinery. In addition, the prediction and validation of regulators of phagocytosis such as the 'exocyst', a macromolecular complex required for exocytosis but not previously implicated in phagocytosis, validates this strategy. In generating this 'systems-based model', we show the power of applying this approach to the study of complex cellular processes and organelles and expect that this detailed model of the phagosome will provide a new framework for studying host-pathogen interactions and innate immunity.

Links

PubMed Online version:10.1038/nature05380

Keywords

Animals; Caenorhabditis elegans; Drosophila Proteins/chemistry; Drosophila Proteins/immunology; Drosophila Proteins/metabolism; Drosophila melanogaster/chemistry; Drosophila melanogaster/immunology; Escherichia coli/immunology; Genomics; Immunity, Innate/immunology; Phagocytosis/immunology; Phagosomes/chemistry; Phagosomes/immunology; Phagosomes/metabolism; Protein Binding; Proteomics; Staphylococcus aureus/immunology; Systems Biology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:COPB2

part_of

GO:0030126: COPI vesicle coat

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:O77285

part_of

GO:0030126: COPI vesicle coat

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:SNAP

located_in

GO:0016020: membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:SNAP

located_in

GO:0031410: cytoplasmic vesicle

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:SNAP

involved_in

GO:0006886: intracellular protein transport

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:SNAP

involved_in

GO:0006891: intra-Golgi vesicle-mediated transport

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:EXOC6

part_of

GO:0000145: exocyst

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:EXOC6

involved_in

GO:0090522: vesicle tethering involved in exocytosis

ECO:0000305: curator inference used in manual assertion

GO:0000145

P

Seeded From UniProt

complete

DROME:EXOC4

part_of

GO:0000145: exocyst

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:EXOC4

involved_in

GO:0090522: vesicle tethering involved in exocytosis

ECO:0000305: curator inference used in manual assertion

GO:0000145

P

Seeded From UniProt

complete

DROME:Q9W0B8

part_of

GO:0030126: COPI vesicle coat

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:EXOC5

part_of

GO:0000145: exocyst

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:EXOC5

involved_in

GO:0090522: vesicle tethering involved in exocytosis

ECO:0000305: curator inference used in manual assertion

GO:0000145

P

Seeded From UniProt

complete

DROME:Q9Y0Y5

part_of

GO:0030126: COPI vesicle coat

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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