title: Drosophila melanogaster cellular repressor of E1A-stimulated genes is a lysosomal protein essential for fly development.
abstract: Mammalian cellular repressor of E1A-stimulated genes is a lysosomal glycoprotein implicated in cellular growth and differentiation. The genome of the fruit fly Drosophila melanogaster encodes a putative orthologue (dCREG), suggesting evolutionarily conserved physiological functions of this protein. In D. melanogaster S2 cells, dCREG was found to localize in lysosomes. Further studies revealed that intracellular dCREG is subject of proteolytic maturation. Processing and turnover could be substantially reduced by RNAi-mediated silencing of cathepsin L. In contrast to mammalian cells, lysosomal delivery of dCREG does not depend on its carbohydrate moiety. Furthermore, depletion of the putative D. melanogaster lysosomal sorting receptor lysosomal enzyme receptor protein did not compromise cellular retention of dCREG. We also investigated the developmental consequences of dCREG ablation in whole D. melanogaster flies. Ubiquitous depletion of dCREG proved lethal at the late pupal stage once a knock-down efficiency of >95% was achieved. These results demonstrate that dCREG is essential for proper completion of fly development.
authors.affiliation: Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Muthgasse 18, A-1190 Vienna, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kowalewski-Nimmerfall
authors.affiliation: Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Muthgasse 18, A-1190 Vienna, Austria.
authors.forename: Philipp
authors.initials: P
authors.lastname: Schähs
authors.affiliation: Department of Chemistry, University of Natural Resources and Life Sciences, Muthgasse 18, A-1190 Vienna, Austria.
authors.forename: Daniel
authors.initials: D
authors.lastname: Maresch
authors.affiliation: Department of Chemistry, University of Natural Resources and Life Sciences, Muthgasse 18, A-1190 Vienna, Austria.
authors.forename: Dubravko
authors.initials: D
authors.lastname: Rendic
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9111, USA; Department of Cell Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9111, USA.
authors.forename: Helmut
authors.initials: H
authors.lastname: Krämer
authors.affiliation: Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Muthgasse 18, A-1190 Vienna, Austria. Electronic address: lukas.mach@boku.ac.at.
authors.forename: Lukas
authors.initials: L
authors.lastname: Mach
keywords: CREG; Cathepsin; Lysosome; Mannose 6-phosphate; Protein targeting; Proteolytic maturation