XBP1s Links the Unfolded Protein Response to the Molecular Architecture of Mature N-Glycans
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 proteos...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2017
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| Online Access: | http://hdl.handle.net/1721.1/106600 https://orcid.org/0000-0002-9438-0643 https://orcid.org/0000-0002-6511-3431 |
| _version_ | 1811079457230815232 |
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| author | Antonopoulos, Aristotelis Haslam, Stuart M. Dell, Anne Dewal, Mahender DiChiara, Andrew Stephen Taylor, Rebecca J. Harmon, Chyleigh J. Shoulders, Matthew D. |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Antonopoulos, Aristotelis Haslam, Stuart M. Dell, Anne Dewal, Mahender DiChiara, Andrew Stephen Taylor, Rebecca J. Harmon, Chyleigh J. Shoulders, Matthew D. |
| author_sort | Antonopoulos, Aristotelis |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:15:19Z |
| format | Article |
| id | mit-1721.1/106600 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:15:19Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1066002022-10-01T02:24:28Z XBP1s Links the Unfolded Protein Response to the Molecular Architecture of Mature N-Glycans Antonopoulos, Aristotelis Haslam, Stuart M. Dell, Anne Dewal, Mahender DiChiara, Andrew Stephen Taylor, Rebecca J. Harmon, Chyleigh J. Shoulders, Matthew D. Massachusetts Institute of Technology. Department of Chemistry Dewal, Mahender DiChiara, Andrew Stephen Taylor, Rebecca J. Harmon, Chyleigh J. Shoulders, Matthew D. 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. Edward Mallinckrodt, Jr. Foundation (Faculty Scholar Award) Mizutani Foundation for Glycoscience (Innovation Grant) Singapore-MIT Alliance for Research and Technology (SMART) Massachusetts Institute of Technology National Institute of Environmental Health Sciences (Grant P30-ES002109) National Institute of Arthritis and Musculoskeletal and Skin Diseases (U.S.) (Grants 1R03AR067503 and F31AR067615) 2017-01-24T19:08:31Z 2017-01-24T19:08:31Z 2015-10 2015-09 Article http://purl.org/eprint/type/JournalArticle 1074-5521 http://hdl.handle.net/1721.1/106600 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. https://orcid.org/0000-0002-9438-0643 https://orcid.org/0000-0002-6511-3431 en_US http://dx.doi.org/10.1016/j.chembiol.2015.09.006 Chemistry and Biology Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Antonopoulos, Aristotelis Haslam, Stuart M. Dell, Anne Dewal, Mahender DiChiara, Andrew Stephen Taylor, Rebecca J. Harmon, Chyleigh J. Shoulders, Matthew D. XBP1s Links the Unfolded Protein Response to the Molecular Architecture of Mature N-Glycans |
| title | XBP1s Links the Unfolded Protein Response to the Molecular Architecture of Mature N-Glycans |
| title_full | XBP1s Links the Unfolded Protein Response to the Molecular Architecture of Mature N-Glycans |
| title_fullStr | XBP1s Links the Unfolded Protein Response to the Molecular Architecture of Mature N-Glycans |
| title_full_unstemmed | XBP1s Links the Unfolded Protein Response to the Molecular Architecture of Mature N-Glycans |
| title_short | XBP1s Links the Unfolded Protein Response to the Molecular Architecture of Mature N-Glycans |
| title_sort | xbp1s links the unfolded protein response to the molecular architecture of mature n glycans |
| url | http://hdl.handle.net/1721.1/106600 https://orcid.org/0000-0002-9438-0643 https://orcid.org/0000-0002-6511-3431 |
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