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PMID:15962002
| Citation |
Khurana, T, Brzostowski, JA and Kimmel, AR (2005) A Rab21/LIM-only/CH-LIM complex regulates phagocytosis via both activating and inhibitory mechanisms. EMBO J. 24:2254-64 |
|---|---|
| Abstract |
We have identified two LIM domain proteins, LimF and ChLim, from Dictyostelium that interact with each other and with the small, Rab5-related, Rab21 GTPase to collectively regulate phagocytosis. To investigate in vivo functions, we generated cell lines that lack or overexpress LimF and ChLim and strains that express activating or inhibiting variants of Rab21. Overexpression of LimF, loss of ChLim, or expression of constitutively active Rab21 increases the rate of phagocytosis above that of wild type. Conversely, loss of LimF, overexpression of ChLim, or expression of a dominant-negative Rab21 inhibits phagocytosis. Our studies using cells carrying multiple mutations in these genes further indicate that ChLim antagonizes the activating function of Rab21-GTP during phagocytosis; in turn, LimF is required for Rab21-GTP function. Finally, we demonstrate that ChLim and LimF localize to the phagocytic cup and phago-lysosomal vesicles. We suggest that LimF, ChLim, and activated Rab21-GTP participate as a novel signaling complex that regulates phagocytic activity. |
| Links |
PubMed PMC1173156 Online version:10.1038/sj.emboj.7600716 |
| Keywords |
Actins/metabolism; Animals; Cell Adhesion; Dictyostelium/genetics; Dictyostelium/physiology; Mutation; Phagocytosis; Protein Structure, Tertiary; Protozoan Proteins/genetics; Protozoan Proteins/metabolism; Signal Transduction; Two-Hybrid System Techniques; rab GTP-Binding Proteins/genetics; rab GTP-Binding Proteins/metabolism |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
|
DICDI:GELA |
part_of |
GO:0001891: phagocytic cup |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | ||
|
DICDI:RAB21 |
colocalizes_with |
GO:0043229: intracellular organelle |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | ||
|
DICDI:RAB21 |
acts_upstream_of_or_within |
GO:0050766: positive regulation of phagocytosis |
ECO:0000316: genetic interaction evidence used in manual assertion |
UniProtKB:Q86I44 |
P |
Seeded From UniProt |
complete | |
|
DICDI:RAB21 |
acts_upstream_of_or_within |
GO:0046847: filopodium assembly |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
DICDI:RAB21 |
acts_upstream_of_or_within |
GO:0050766: positive regulation of phagocytosis |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
DICDI:RAB21 |
acts_upstream_of_or_within |
GO:0030866: cortical actin cytoskeleton organization |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
DICDI:RAB21 |
NOT|acts_upstream_of_or_within |
GO:0006907: pinocytosis |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
DICDI:RAB21 |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:Q55GV9 |
F |
Seeded From UniProt |
complete | |
|
DICDI:RAB21 |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:Q86I44 |
F |
Seeded From UniProt |
complete | |
|
DICDI:LIMCH |
located_in |
GO:0045335: phagocytic vesicle |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | ||
|
DICDI:LIMCH |
located_in |
GO:0005829: cytosol |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | ||
|
DICDI:LIMCH |
located_in |
GO:0030863: cortical cytoskeleton |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | ||
|
DICDI:LIMCH |
located_in |
GO:0001891: phagocytic cup |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | ||
|
DICDI:LIMCH |
located_in |
GO:0005938: cell cortex |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | ||
|
DICDI:LIMCH |
acts_upstream_of_or_within |
GO:0050765: negative regulation of phagocytosis |
ECO:0000316: genetic interaction evidence used in manual assertion |
UniProtKB:Q86I44 |
P |
Seeded From UniProt |
complete | |
|
DICDI:LIMCH |
NOT|enables |
GO:0030695: GTPase regulator activity |
ECO:0000316: genetic interaction evidence used in manual assertion |
UniProtKB:P34142 |
F |
Seeded From UniProt |
complete | |
|
DICDI:LIMCH |
acts_upstream_of_or_within |
GO:0046847: filopodium assembly |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
DICDI:LIMCH |
acts_upstream_of_or_within |
GO:0050765: negative regulation of phagocytosis |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
DICDI:LIMCH |
NOT|acts_upstream_of_or_within |
GO:0006907: pinocytosis |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
DICDI:LIMCH |
enables |
GO:0008270: zinc ion binding |
ECO:0000250: sequence similarity evidence used in manual assertion |
F |
Seeded From UniProt |
complete | ||
|
DICDI:LIMCH |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:P34142 |
F |
Seeded From UniProt |
complete | |
|
DICDI:LIMCH |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:Q86I44 |
F |
Seeded From UniProt |
complete | |
|
DICDI:LIMF |
colocalizes_with |
GO:0001891: phagocytic cup |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | ||
|
DICDI:LIMF |
acts_upstream_of_or_within |
GO:0050766: positive regulation of phagocytosis |
ECO:0000316: genetic interaction evidence used in manual assertion |
UniProtKB:Q55GV9 |
P |
Seeded From UniProt |
complete | |
|
DICDI:LIMF |
NOT|enables |
GO:0030695: GTPase regulator activity |
ECO:0000316: genetic interaction evidence used in manual assertion |
UniProtKB:P34142 |
F |
Seeded From UniProt |
complete | |
|
DICDI:LIMF |
acts_upstream_of_or_within |
GO:0046847: filopodium assembly |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
DICDI:LIMF |
acts_upstream_of_or_within |
GO:0050766: positive regulation of phagocytosis |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
DICDI:LIMF |
NOT|acts_upstream_of_or_within |
GO:0006907: pinocytosis |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
DICDI:LIMF |
enables |
GO:0008270: zinc ion binding |
ECO:0000250: sequence similarity evidence used in manual assertion |
F |
Seeded From UniProt |
complete | ||
|
DICDI:LIMF |
acts_upstream_of_or_within |
GO:0007015: actin filament organization |
ECO:0000250: sequence similarity evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
DICDI:LIMF |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:P34142 |
F |
Seeded From UniProt |
complete | |
|
DICDI:LIMF |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:Q55GV9 |
F |
Seeded From UniProt |
complete | |
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