A P-glycoprotein protects Caenorhabditis elegans against natural toxins

EMBO J. 1995 May 1;14(9):1858-66.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • ATP Binding Cassette Transporter, Subfamily B / metabolism*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Caenorhabditis elegans / drug effects*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Chloroquine / pharmacology
  • Colchicine / pharmacology
  • DNA, Helminth / genetics
  • Drug Resistance / genetics
  • Genes, Helminth
  • Helminth Proteins / genetics
  • Helminth Proteins / metabolism*
  • Microscopy, Electron
  • Molecular Sequence Data
  • Mutation
  • Tissue Distribution
  • Toxins, Biological / toxicity*

Substances

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Caenorhabditis elegans Proteins
  • DNA, Helminth
  • Helminth Proteins
  • PGP-3 protein, C elegans
  • Toxins, Biological
  • Chloroquine
  • Colchicine