Journal article
Regulation of BMP4/Dpp retrotranslocation and signaling by deglycosylation
- Galeone, Antonio Department of Biosciences, University of Milan, Milan, Italy
- Adams, Joshua M Medical Scientist Training Program, Baylor College of Medicine, Houston, United States
- Matsuda, Shinya ORCID Biozentrum, University of Basel, Basel, Switzerland
- Presa, Maximiliano F The Jackson Laboratory, Bar Harbor, United States
- Pandey, Ashutosh Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States
- Han, Seung Yeop Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States
- Tachida, Yuriko T-CiRA joint program, Kanagawa, Japan
- Hirayama, Hiroto T-CiRA joint program, Kanagawa, Japan
- Vaccari, Thomas Department of Biosciences, University of Milan, Milan, Italy
- Suzuki, Tadashi T-CiRA joint program, Kanagawa, Japan
- Lutz, Cathleen M The Jackson Laboratory, Bar Harbor, United States
- Affolter, Markus ORCID Biozentrum, University of Basel, Basel, Switzerland
- Zuberi, Aamir The Jackson Laboratory, Bar Harbor, United States
- Jafar-Nejad, Hamed ORCID Program in Developmental Biology, Baylor College of Medicine, Houston, United States
- 2020-7-28
Published in:
- eLife. - eLife Sciences Publications, Ltd. - 2020, vol. 9
General Biochemistry, Genetics and Molecular Biology
General Immunology and Microbiology
General Neuroscience
General Medicine
English
During endoplasmic reticulum-associated degradation (ERAD), the cytoplasmic enzyme N -glycanase 1 (NGLY1) is proposed to remove N -glycans from misfolded N -glycoproteins after their retrotranslocation from the ER to the cytosol. We previously reported that NGLY1 regulates Drosophila BMP signaling in a tissue-specific manner (Galeone et al., 2017). Here, we establish the Drosophila Dpp and its mouse ortholog BMP4 as biologically relevant targets of NGLY1 and find, unexpectedly, that NGLY1-mediated deglycosylation of misfolded BMP4 is required for its retrotranslocation. Accumulation of misfolded BMP4 in the ER results in ER stress and prompts the ER recruitment of NGLY1. The ER-associated NGLY1 then deglycosylates misfolded BMP4 molecules to promote their retrotranslocation and proteasomal degradation, thereby allowing properly-folded BMP4 molecules to proceed through the secretory pathway and activate signaling in other cells. Our study redefines the role of NGLY1 during ERAD and suggests that impaired BMP4 signaling might underlie some of the NGLY1 deficiency patient phenotypes.
- Language
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- English
- Open access status
- gold
- Identifiers
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- DOI 10.7554/elife.55596
- ISSN 2050-084X
- Persistent URL
- https://sonar.ch/global/documents/64209
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