Drosophila melanogaster cellular repressor of E1A-stimulated genes is a lysosomal protein essential for fly development

Elisabeth Kowalewski-Nimmerfall, Philipp Schähs, Daniel Maresch, Dubravko Rendic, Helmut Krämer, Lukas Mach

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2900-2912
Number of pages13
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1843
Issue number12
DOIs
StatePublished - Aug 27 2014

Keywords

  • CREG
  • Cathepsin
  • Lysosome
  • Mannose 6-phosphate
  • Protein targeting
  • Proteolytic maturation

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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