Tissue-specific regulation of BMP signaling by Drosophila N-glycanase 1
- Baylor College of Medicine, United States
- RIKEN Global Research Cluster, Japan
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.
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Author details
Funding
Grace Wilsey Foundation (Research Grant)
- Tadashi Suzuki
- Hamed Jafar-Nejad
National Institutes of Health (R01GM084135 R01DK109982)
- Hamed Jafar-Nejad
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Galeone et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Tissue-specific regulation of BMP signaling by Drosophila N-glycanase 1
eLife 6:e27612.
https://doi.org/10.7554/eLife.27612
Further reading
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- Developmental Biology
Mutations in an enzyme involved in protein degradation affect a signaling pathway that stimulates the development of the digestive tract.
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Disease-causing mutations in the signaling protein BMP4 impair its secretion, but only when it is made as a homodimer.
