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PMID:15962002

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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

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

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q55GV9

F

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: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

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: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

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q86I44

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

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:0005829: cytosol

ECO:0000314: direct assay evidence used in manual assertion

C

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

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

enables

GO:0008270: zinc ion binding

ECO:0000250: sequence similarity evidence used in manual assertion

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:0005938: cell cortex

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

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

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

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

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q86I44

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

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

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

enables

GO:0008270: zinc ion binding

ECO:0000250: sequence similarity evidence used in manual assertion

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: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:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q55GV9

P

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

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

See also

References

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