XBP1s Links the Unfolded Protein Response to the Molecular Architecture of Mature N-Glycans
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Shoulders_Xbp1s links.pdf
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Author(s)
Antonopoulos, Aristotelis
Haslam, Stuart M.
Dell, Anne
Dewal, Mahender
DiChiara, Andrew Stephen
Taylor, Rebecca J.
Harmon, Chyleigh J.
Shoulders, Matthew D.
Date Issued
October 2015
Journal
Chemistry and Biology
Publisher
Elsevier
Citation
Dewal, Mahender B. et al. “XBP1s Links the Unfolded Protein Response to the Molecular Architecture of Mature N-Glycans.” Chemistry & Biology 22.10 (2015): 1301–1312.
Version
Author's final manuscript
Abstract
The molecular architecture of the mature N-glycome is dynamic, with consequences for both normal and pathologic processes. Elucidating cellular mechanisms that modulate the N-linked glycome is, therefore, crucial. The unfolded protein response (UPR) is classically responsible for maintaining proteostasis in the secretory pathway by defining levels of chaperones and quality control proteins. Here, we employ chemical biology methods for UPR regulation to show that stress-independent activation of the UPR’s XBP1s transcription factor also induces a panel of N-glycan maturation-related enzymes. The downstream consequence is a distinctive shift toward specific hybrid and complex N-glycans on N-glycoproteins produced from XBP1s-activated cells, which we characterize by mass spectrometry. Pulse-chase studies attribute this shift specifically to altered N-glycan processing, rather than to changes in degradation or secretion rates. Our findings implicate XBP1s in a new role for N-glycoprotein biosynthesis, unveiling an important link between intracellular stress responses and the molecular architecture of extracellular N-glycoproteins.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.chembiol.2015.09.006
