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PMID:17151602
| 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 |
| edit table |
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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