The Uncovered Function of the Drosophila GBA1a-Encoded Protein

Or Cabasso, Sumit Paul, Gali Maor, Metsada Pasmanik-Chor, Wouter Kallemeijn, Johannes Aerts, Mia Horowitz

Research output: Contribution to journalArticlepeer-review


Human GBA1 encodes lysosomal acid β-glucocerebrosidase (GCase), which hydrolyzes cleavage of the beta-glucosidic linkage of glucosylceramide (GlcCer). Mutations in this gene lead to reduced GCase activity, accumulation of glucosylceramide and glucosylsphingosine, and development of Gaucher disease (GD). Drosophila melanogaster has two GBA1 orthologs. Thus far, GBA1b was documented as a bone fide GCase-encoding gene, while the role of GBA1a encoded protein remained unclear. In the present study, we characterized a mutant variant of the fly GBA1a, which underwent ERAD and mildly activated the UPR machinery. RNA-seq analyses of homozygous mutant flies revealed upregulation of inflammation-associated as well as of cell-cycle related genes and reduction in programmed cell death (PCD)-associated genes, which was confirmed by qRT-PCR. We also observed compromised cell death in the midgut of homozygous larvae and a reduction in pupation. Our results strongly indicated that GBA1a-encoded protein plays a role in midgut maturation during larvae development.

Original languageEnglish
Article number630
Pages (from-to)1-20
Number of pages20
Issue number3
StatePublished - 12 Mar 2021


  • acid β-glucocerebrosidase
  • Gaucher disease
  • GBA1
  • inflammation
  • unfolded protein response


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