Tissue-specific regulation of BMP signaling by Drosophila N-glycanase 1

Elife. 2017 Aug 4;6:e27612. doi: 10.7554/eLife.27612.

Abstract

Mutations in the human N-glycanase 1 (NGLY1) cause a rare, multisystem congenital disorder with global developmental delay. However, the mechanisms by which NGLY1 and its homologs regulate embryonic development are not known. Here we show that Drosophila Pngl encodes an N-glycanase and exhibits a high degree of functional conservation with human NGLY1. Loss of Pngl results in developmental midgut defects reminiscent of midgut-specific loss of BMP signaling. Pngl mutant larvae also exhibit a severe midgut clearance defect, which cannot be fully explained by impaired BMP signaling. Genetic experiments indicate that Pngl is primarily required in the mesoderm during Drosophila development. Loss of Pngl results in a severe decrease in the level of Dpp homodimers and abolishes BMP autoregulation in the visceral mesoderm mediated by Dpp and Tkv homodimers. Thus, our studies uncover a novel mechanism for the tissue-specific regulation of an evolutionarily conserved signaling pathway by an N-glycanase enzyme.

Keywords: BMP signaling; D. melanogaster; Drosophila; NGLY1; developmental biology; midgut; stem cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins / metabolism*
  • Drosophila / embryology*
  • Drosophila / enzymology*
  • Drosophila Proteins / metabolism*
  • Gastrointestinal Tract / embryology
  • Gene Expression Regulation
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism
  • Receptors, Cell Surface / metabolism
  • Signal Transduction

Substances

  • Bone Morphogenetic Proteins
  • Drosophila Proteins
  • Receptors, Cell Surface
  • dpp protein, Drosophila
  • tkv protein, Drosophila
  • Protein-Serine-Threonine Kinases
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase