Multidrug resistance-associated protein MRP-1 regulates dauer diapause by its export activity in Caenorhabditis elegans

Tomoko Yabe, Norio Suzuki, Tatsuhiko Furukawa, Takeshi Ishihara, Isao Katsura

Research output: Contribution to journalArticle

35 Citations (Scopus)

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-β 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.

Original languageEnglish
Pages (from-to)3197-3207
Number of pages11
JournalDevelopment
Volume132
Issue number14
DOIs
Publication statusPublished - Jul 1 2005

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Multidrug Resistance-Associated Proteins
Caenorhabditis elegans
Larva
Insulin
Caenorhabditis elegans Proteins
Genes
Phenotype
Mutation
Growth
Life Cycle Stages
Drug Resistance
Neoplasms
Cell Membrane
multidrug resistance-associated protein 1

All Science Journal Classification (ASJC) codes

  • Anatomy
  • Cell Biology

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Multidrug resistance-associated protein MRP-1 regulates dauer diapause by its export activity in Caenorhabditis elegans. / Yabe, Tomoko; Suzuki, Norio; Furukawa, Tatsuhiko; Ishihara, Takeshi; Katsura, Isao.

In: Development, Vol. 132, No. 14, 01.07.2005, p. 3197-3207.

Research output: Contribution to journalArticle

Yabe, Tomoko ; Suzuki, Norio ; Furukawa, Tatsuhiko ; Ishihara, Takeshi ; Katsura, Isao. / Multidrug resistance-associated protein MRP-1 regulates dauer diapause by its export activity in Caenorhabditis elegans. In: Development. 2005 ; Vol. 132, No. 14. pp. 3197-3207.
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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-β 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.",
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