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PMID:18039932

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Citation

Jeon, TJ, Lee, DJ, Lee, S, Weeks, G and Firtel, RA (2007) Regulation of Rap1 activity by RapGAP1 controls cell adhesion at the front of chemotaxing cells. J. Cell Biol. 179:833-43

Abstract

Spatial and temporal regulation of Rap1 is required for proper myosin assembly and cell adhesion during cell migration in Dictyostelium discoideum. Here, we identify a Rap1 guanosine triphosphatase-activating protein (GAP; RapGAP1) that helps mediate cell adhesion by negatively regulating Rap1 at the leading edge. Defects in spatial regulation of the cell attachment at the leading edge in rapGAP1- (null) cells or cells overexpressing RapGAP1 (RapGAP1(OE)) lead to defective chemotaxis. rapGAP1- cells have extended chemoattractant-mediated Rap1 activation kinetics and decreased MyoII assembly, whereas RapGAP1(OE) cells show reciprocal phenotypes. We see that RapGAP1 translocates to the cell cortex in response to chemoattractant stimulation and localizes to the leading edge of chemotaxing cells via an F-actin-dependent pathway. RapGAP1 localization is negatively regulated by Ctx, an F-actin bundling protein that functions during cytokinesis. Loss of Ctx leads to constitutive and uniform RapGAP1 cortical localization. We suggest that RapGAP1 functions in the spatial and temporal regulation of attachment sites through MyoII assembly via regulation of Rap1-guanosine triphosphate.

Links

PubMed PMC2099181 Online version:10.1083/jcb.200705068

Keywords

Actins/metabolism; Animals; Cell Adhesion; Cell Movement; Chemotaxis; Dictyostelium/cytology; Dictyostelium/enzymology; Enzyme Activation; GTPase-Activating Proteins/chemistry; GTPase-Activating Proteins/metabolism; Green Fluorescent Proteins/metabolism; Kinetics; Myosin Type II/metabolism; Protein Structure, Tertiary; Protein Transport; Pseudopodia/enzymology; Recombinant Fusion Proteins/metabolism; Subcellular Fractions/enzymology; Substrate Specificity; rap1 GTP-Binding Proteins/metabolism

Significance

Annotations

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

DICDI:RAPA

acts_upstream_of_or_within

GO:0030838: positive regulation of actin filament polymerization

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

DICDI:CTXA

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q75J96

F

Seeded From UniProt

complete

DICDI:CTXA

acts_upstream_of_or_within

GO:0045184: establishment of protein localization

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q550R2

P

Seeded From UniProt

complete

DICDI:CTXA

acts_upstream_of_or_within

GO:0043087: regulation of GTPase activity

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q550R2

P

Seeded From UniProt

complete

DICDI:CTXB

acts_upstream_of_or_within

GO:0045184: establishment of protein localization

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q54HG2

P

Seeded From UniProt

complete

DICDI:CTXB

acts_upstream_of_or_within

GO:0043087: regulation of GTPase activity

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q54HG2

P

Seeded From UniProt

complete

DICDI:RGAP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q54HG2

F

Seeded From UniProt

complete

DICDI:RGAP1

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DICDI:RGAP1

acts_upstream_of_or_within

GO:0031589: cell-substrate adhesion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DICDI:RGAP1

acts_upstream_of_or_within

GO:0030837: negative regulation of actin filament polymerization

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

DICDI:RGAP1

acts_upstream_of_or_within

GO:0007163: establishment or maintenance of cell polarity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DICDI:RGAP1

enables

GO:0005096: GTPase activator activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DICDI:RGAP1

located_in

GO:0031252: cell leading edge

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DICDI:RGAP1

colocalizes_with

GO:0005938: cell cortex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DICDI:RGAP1

involved_in

GO:0051591: response to cAMP

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DICDI:RGAP1

acts_upstream_of_or_within

GO:0051270: regulation of cellular component movement

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DICDI:RGAP1

acts_upstream_of_or_within

GO:0043547: positive regulation of GTPase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DICDI:RGAP1

acts_upstream_of_or_within

GO:0043520: regulation of myosin II filament assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DICDI:RGAP1

involved_in

GO:0090630: activation of GTPase activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

See also

References

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