Genetic analysis of lysosomal trafficking in Caenorhabditis elegans.
The intestinal cells of Caenorhabditis elegans embryos contain prominent, birefringent gut granules that we show are lysosome-related organelles. Gut granules are labeled by lysosomal markers, and their formation is disrupted in embryos depleted of AP-3 subunits, VPS-16, and VPS-41. We define a class of gut granule loss (glo) mutants that are defective in gut granule biogenesis. We show that the glo-1 gene encodes a predicted Rab GTPase that localizes to lysosome-related gut granules in the intestine and that glo-4 encodes a possible GLO-1 guanine nucleotide exchange factor. These and other glo genes are homologous to genes implicated in the biogenesis of specialized, lysosome-related organelles such as melanosomes in mammals and pigment granules in Drosophila. The glo mutants thus provide a simple model system for the analysis of lysosome-related organelle biogenesis in animal cells.
Hermann
Greg J
GJ
Department of Biology, Lewis and Clark College, Portland, OR 97219, USA. hermann@lclark.edu
Schroeder
Lena K
LK
Hieb
Caroline A
CA
Kershner
Aaron M
AM
Rabbitts
Beverley M
BM
Fonarev
Paul
P
Grant
Barth D
BD
Priess
James R
JR
D000165:Acridine Orange / Q000494:pharmacology; D033963:Adaptor Protein Complex 3; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D049628:Body Size; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics; D004330:Drosophila; D004843:Epistasis, Genetic; D020558:GTP Phosphohydrolases / Q000378:metabolism; D017238:Genes, Helminth; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D020460:Melanosomes / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D021381:Protein Transport; D017386:Sequence Homology, Amino Acid; D013696:Temperature; D014157:Transcription Factors / Q000235:genetics; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
D033963:Adaptor Protein Complex 3; D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; C505597:Glo-4 protein, C elegans; D020662:Guanine Nucleotide Exchange Factors; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D020558:GTP Phosphohydrolases; C505598:Glo-1 protein, C elegans; D020691:rab GTP-Binding Proteins; D000165:Acridine Orange