Role of the Caenorhabditis elegans multidrug resistance gene, mrp-4, in gut granule differentiation.
Caenorhabditis elegans gut granules are lysosome-related organelles with birefringent contents. mrp-4, which encodes an ATP-binding cassette (ABC) transporter homologous to mammalian multidrug resistance proteins, functions in the formation of gut granule birefringence. mrp-4(-) embryos show a delayed appearance of birefringent material in the gut granule but otherwise appear to form gut granules properly. mrp-4(+) activity is required for the extracellular mislocalization of birefringent material, body-length retraction, and NaCl sensitivity, phenotypes associated with defective gut granule biogenesis exhibited by embryos lacking the activity of GLO-1/Rab38, a putative GLO-1 guanine nucleotide exchange factor GLO-4, and the AP-3 complex. Multidrug resistance protein (MRP)-4 localizes to the gut granule membrane, consistent with it playing a direct role in the transport of molecules that compose and/or facilitate the formation of birefringent crystals within the gut granule. However, MRP-4 is also present in oocytes and early embryos, and our genetic analyses indicate that its site of action in the formation of birefringent material may not be limited to just the gut granule in embryos. In a search for genes that function similarly to mrp-4(+), we identified WHT-2, another ABC transporter that acts in parallel to MRP-4 for the formation of birefringent material in the gut granule.
Currie
Erin
E
Department of Biology, Lewis & Clark College, Portland, Oregon 97219, USA.
King
Brian
B
Lawrenson
Andrea L
AL
Schroeder
Lena K
LK
Kershner
Aaron M
AM
Hermann
Greg J
GJ
D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D001718:Birefringence; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism; D018509:DNA, Helminth / Q000235:genetics; D004064:Digestive System / Q000196:embryology / Q000378:metabolism; D018432:Drug Resistance, Multiple / Q000235:genetics; D017238:Genes, Helminth; D008247:Lysosomes / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D018509:DNA, Helminth; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D020691:rab GTP-Binding Proteins; C505598:Glo-1 protein, C elegans