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PMID:15983401

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Citation

Yabe, T, Suzuki, N, Furukawa, T, Ishihara, T and Katsura, I (2005) Multidrug resistance-associated protein MRP-1 regulates dauer diapause by its export activity in Caenorhabditis elegans. Development 132:3197-207

Abstract

Multidrug resistance-associated proteins (MRPs), when overexpressed, confer drug resistance to cancer cells by exporting anti-cancer agents through the cell membrane, but their role in animal development has not been elucidated. Here we show that an MRP homolog regulates larval development in the nematode Caenorhabditis elegans. C. elegans forms a special third-stage larva called a dauer larva under conditions inappropriate for growth. By contrast, we found that mutants in mrp-1, an MRP homolog gene, form dauer larvae even under conditions appropriate for growth, in the background of certain mutations that partially block the insulin signaling pathway. A functional mrp-1::GFP gene was shown to be expressed in many tissues, and the wild-type mrp-1 gene must be expressed in multiple tissues for a wild-type phenotype. Human MRP1 could substitute for C. elegans MRP-1 in dauer larva regulation, and an inhibitor of the human MRP1 transport activity impaired this function, showing that export activity is required for normal dauer larva regulation. Epistasis studies revealed that MRP-1 acts in neither the TGF-beta nor the cGMP signaling pathway. mrp-1 mutations enhanced the dauer-constitutive phenotype of mutants in the insulin signaling pathway more strongly than that in other pathways. Thus, MRP-1, through its export activity, supports the induction of the normal (non-dauer) life cycle by the insulin signaling pathway.

Links

PubMed Online version:10.1242/dev.01909

Keywords

Animals; Caenorhabditis elegans/growth & development; Genes, Reporter; Humans; Larva/genetics; Larva/growth & development; Mutation; P-Glycoprotein/genetics; P-Glycoprotein/physiology; Protein Isoforms/genetics; Protein Isoforms/physiology; Protein Transport/physiology; Recombinant Fusion Proteins/genetics; Recombinant Fusion Proteins/physiology; Sequence Analysis, DNA

Significance

Annotations

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

CAEEL:Q3S1M2

located_in

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:Q3S1M2

involved_in

GO:0097501: stress response to metal ion

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00006767

P

Seeded From UniProt

complete

CAEEL:Q3S1M2

involved_in

GO:0040024: dauer larval development

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00006767

P

Seeded From UniProt

complete

CAEEL:Q7YZW1

located_in

GO:0005887: integral component of plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:Q7YZW1

involved_in

GO:0097501: stress response to metal ion

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00006767

P

Seeded From UniProt

complete

CAEEL:Q7YZW1

involved_in

GO:0040024: dauer larval development

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00006767

P

Seeded From UniProt

complete

CAEEL:Q8MQ16

located_in

GO:0005887: integral component of plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:Q8MQ16

involved_in

GO:0097501: stress response to metal ion

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00006767

P

Seeded From UniProt

complete

CAEEL:Q8MQ16

involved_in

GO:0040024: dauer larval development

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00006767

P

Seeded From UniProt

complete

CAEEL:Q95QE2

located_in

GO:0005887: integral component of plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:Q95QE2

involved_in

GO:0097501: stress response to metal ion

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00006767

P

Seeded From UniProt

complete

CAEEL:Q95QE2

involved_in

GO:0040024: dauer larval development

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00006767

P

Seeded From UniProt

complete


See also

References

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