Back
Regulation of BMP4/Dpp retrotranslocation and signaling by deglycosylation.
Journal article

Regulation of BMP4/Dpp retrotranslocation and signaling by deglycosylation.

  • Galeone A Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.
  • Adams JM Program in Developmental Biology, Baylor College of Medicine, Houston, United States.
  • Matsuda S Biozentrum, University of Basel, Basel, Switzerland.
  • Presa MF The Jackson Laboratory, Bar Harbor, United States.
  • Pandey A Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.
  • Han SY Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.
  • Tachida Y Glycometabolome Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Saitama, Japan.
  • Hirayama H Glycometabolome Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Saitama, Japan.
  • Vaccari T Department of Biosciences, University of Milan, Milan, Italy.
  • Suzuki T Glycometabolome Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Saitama, Japan.
  • Lutz CM The Jackson Laboratory, Bar Harbor, United States.
  • Affolter M Biozentrum, University of Basel, Basel, Switzerland.
  • Zuberi A The Jackson Laboratory, Bar Harbor, United States.
  • Jafar-Nejad H Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.
Show more…
  • 2020-07-29
Published in:
  • eLife. - 2020
BMP signaling
D. melanogaster
ERAD
N-glycosylation
NGLY1
cell biology
deglycosylation
developmental biology
mouse
retrotranslocation
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
  • English
Open access status
gold
Identifiers
Persistent URL
https://sonar.rero.ch/global/documents/90891
Statistics
Document views: 13 File downloads: