Abstract
P-glycoproteins can cause resistance of mammalian tumor cells to chemotherapeutic drugs. They belong to an evolutionarily well-conserved family of ATP binding membrane transporters. Four P-glycoprotein gene homologs have been found in the nematode Caenorhabditis elegans; this report describes the functional analysis of two. We found that PGP-3 is expressed in both the apical membrane of the excretory cell and in the apical membrane of intestinal cells, whereas PGP-1 is expressed only in the apical membrane of the intestinal cells and the intestinal valve. By transposon-mediated deletion mutagenesis we generated nematode strains with deleted P-glycoprotein genes and found that the pgp-3 deletion mutant, but not the pgp-1 mutant, is sensitive to both colchicine and chloroquine. Our results suggest that soil nematodes have P-glycoproteins to protect themselves against toxic compounds made by plants and microbes in the rhizosphere.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B / genetics
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ATP Binding Cassette Transporter, Subfamily B / metabolism*
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
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Animals
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Animals, Genetically Modified
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Base Sequence
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Caenorhabditis elegans / drug effects*
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans / metabolism*
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism*
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Chloroquine / pharmacology
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Colchicine / pharmacology
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DNA, Helminth / genetics
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Drug Resistance / genetics
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Genes, Helminth
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Helminth Proteins / genetics
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Helminth Proteins / metabolism*
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Microscopy, Electron
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Molecular Sequence Data
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Mutation
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Tissue Distribution
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Toxins, Biological / toxicity*
Substances
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ATP Binding Cassette Transporter, Subfamily B
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Caenorhabditis elegans Proteins
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DNA, Helminth
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Helminth Proteins
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PGP-3 protein, C elegans
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Toxins, Biological
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Chloroquine
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Colchicine