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PMID:15525675

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Citation

Pellis-van Berkel, W, Verheijen, MH, Cuppen, E, Asahina, M, de Rooij, J, Jansen, G, Plasterk, RH, Bos, JL and Zwartkruis, FJ (2005) Requirement of the Caenorhabditis elegans RapGEF pxf-1 and rap-1 for epithelial integrity. Mol. Biol. Cell 16:106-16

Abstract

The Rap-pathway has been implicated in various cellular processes but its exact physiological function remains poorly defined. Here we show that the Caenorhabditis elegans homologue of the mammalian guanine nucleotide exchange factors PDZ-GEFs, PXF-1, specifically activates Rap1 and Rap2. Green fluorescent protein (GFP) reporter constructs demonstrate that sites of pxf-1 expression include the hypodermis and gut. Particularly striking is the oscillating expression of pxf-1 in the pharynx during the four larval molts. Deletion of the catalytic domain from pxf-1 leads to hypodermal defects, resulting in lethality. The cuticle secreted by pxf-1 mutants is disorganized and can often not be shed during molting. At later stages, hypodermal degeneration is seen and animals that reach adulthood frequently die with a burst vulva phenotype. Importantly, disruption of rap-1 leads to a similar, but less severe phenotype, which is enhanced by the simultaneous removal of rap-2. In addition, the lethal phenotype of pxf-1 can be rescued by expression of an activated version of rap-1. Together these results demonstrate that the pxf-1/rap pathway in C. elegans is required for maintenance of epithelial integrity, in which it probably functions in polarized secretion.

Links

PubMed PMC539156 Online version:10.1091/mbc.E04-06-0492

Keywords

Animals; Animals, Genetically Modified; Caenorhabditis elegans; Caenorhabditis elegans Proteins/metabolism; Caenorhabditis elegans Proteins/physiology; Catalytic Domain; Cell Proliferation; DNA, Complementary/metabolism; Epithelium/metabolism; GTP Phosphohydrolases/metabolism; Genes, Reporter; Genotype; Green Fluorescent Proteins/metabolism; Guanine Nucleotide Exchange Factors/metabolism; Guanine Nucleotide Exchange Factors/physiology; Homozygote; Microscopy, Electron; Microscopy, Fluorescence; Models, Genetic; Mutation; Phenotype; rap1 GTP-Binding Proteins/physiology

Significance

Annotations

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

CAEEL:F5GUA2

involved_in

GO:0018996: molting cycle, collagen and cuticulin-based cuticle

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00239356

P

Seeded From UniProt

complete

CAEEL:F5GUA2

located_in

GO:0060102: collagen and cuticulin-based cuticle extracellular matrix

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:F5GUA2

involved_in

GO:0008544: epidermis development

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00239356

P

Seeded From UniProt

complete

CAEEL:F5GUA2

enables

GO:0005085: guanyl-nucleotide exchange factor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:F5GUA2

involved_in

GO:0040002: collagen and cuticulin-based cuticle development

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00239356

P

Seeded From UniProt

complete

CAEEL:G5ECB8

involved_in

GO:0018996: molting cycle, collagen and cuticulin-based cuticle

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00239356

P

Seeded From UniProt

complete

CAEEL:G5ECB8

located_in

GO:0060102: collagen and cuticulin-based cuticle extracellular matrix

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:G5ECB8

involved_in

GO:0008544: epidermis development

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00239356

P

Seeded From UniProt

complete

CAEEL:G5ECB8

enables

GO:0005085: guanyl-nucleotide exchange factor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:G5ECB8

involved_in

GO:0040002: collagen and cuticulin-based cuticle development

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00239356

P

Seeded From UniProt

complete

CAEEL:G5ECE2

involved_in

GO:0018996: molting cycle, collagen and cuticulin-based cuticle

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00239356

P

Seeded From UniProt

complete

CAEEL:G5ECE2

located_in

GO:0060102: collagen and cuticulin-based cuticle extracellular matrix

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:G5ECE2

involved_in

GO:0008544: epidermis development

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00239356

P

Seeded From UniProt

complete

CAEEL:G5ECE2

enables

GO:0005085: guanyl-nucleotide exchange factor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:G5ECE2

involved_in

GO:0040002: collagen and cuticulin-based cuticle development

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00239356

P

Seeded From UniProt

complete

CAEEL:RPGF

involved_in

GO:0018996: molting cycle, collagen and cuticulin-based cuticle

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00239356

P

Seeded From UniProt

complete

CAEEL:RPGF

located_in

GO:0060102: collagen and cuticulin-based cuticle extracellular matrix

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:RPGF

involved_in

GO:0008544: epidermis development

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00239356

P

Seeded From UniProt

complete

CAEEL:RPGF

enables

GO:0005085: guanyl-nucleotide exchange factor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:RPGF

involved_in

GO:0040002: collagen and cuticulin-based cuticle development

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00239356

P

Seeded From UniProt

complete

CAEEL:G5EEE0

involved_in

GO:0018996: molting cycle, collagen and cuticulin-based cuticle

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00239356

P

Seeded From UniProt

complete

CAEEL:G5EEE0

located_in

GO:0060102: collagen and cuticulin-based cuticle extracellular matrix

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:G5EEE0

involved_in

GO:0008544: epidermis development

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00239356

P

Seeded From UniProt

complete

CAEEL:G5EEE0

enables

GO:0005085: guanyl-nucleotide exchange factor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:G5EEE0

involved_in

GO:0040002: collagen and cuticulin-based cuticle development

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00239356

P

Seeded From UniProt

complete

CAEEL:O17599

involved_in

GO:0008544: epidermis development

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00004307

P

Seeded From UniProt

complete

CAEEL:O17599

involved_in

GO:0040002: collagen and cuticulin-based cuticle development

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00004307

P

Seeded From UniProt

complete

CAEEL:RAP1

involved_in

GO:0008544: epidermis development

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBGene00004308

P

Seeded From UniProt

complete

CAEEL:RAP1

involved_in

GO:0008544: epidermis development

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00239429

P

Seeded From UniProt

complete

CAEEL:RAP1

enables

GO:0003924: GTPase activity

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:P18613

F

Seeded From UniProt

complete

CAEEL:RAP1

involved_in

GO:0040002: collagen and cuticulin-based cuticle development

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00239429

P

Seeded From UniProt

complete

CAEEL:RAP1

involved_in

GO:0040002: collagen and cuticulin-based cuticle development

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00004308

P

Seeded From UniProt

complete


See also

References

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