Cargando…
Ufbp1 promotes plasma cell development and ER expansion by modulating distinct branches of UPR
The IRE1α/XBP1 branch of unfolded protein response (UPR) pathway has a critical function in endoplasmic reticulum (ER) expansion in plasma cells via unknown mechanisms; interestingly, another UPR branch, PERK, is suppressed during plasma cell development. Here we show that Ufbp1, a target and cofact...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403283/ https://www.ncbi.nlm.nih.gov/pubmed/30842412 http://dx.doi.org/10.1038/s41467-019-08908-5 |
_version_ | 1783400560762814464 |
---|---|
author | Zhu, Huabin Bhatt, Brinda Sivaprakasam, Sathish Cai, Yafei Liu, Siyang Kodeboyina, Sai Karthik Patel, Nikhil Savage, Natasha M. Sharma, Ashok Kaufman, Randal J. Li, Honglin Singh, Nagendra |
author_facet | Zhu, Huabin Bhatt, Brinda Sivaprakasam, Sathish Cai, Yafei Liu, Siyang Kodeboyina, Sai Karthik Patel, Nikhil Savage, Natasha M. Sharma, Ashok Kaufman, Randal J. Li, Honglin Singh, Nagendra |
author_sort | Zhu, Huabin |
collection | PubMed |
description | The IRE1α/XBP1 branch of unfolded protein response (UPR) pathway has a critical function in endoplasmic reticulum (ER) expansion in plasma cells via unknown mechanisms; interestingly, another UPR branch, PERK, is suppressed during plasma cell development. Here we show that Ufbp1, a target and cofactor of the ufmylation pathway, promotes plasma cell development by suppressing the activation of PERK. By contrast, the IRE1α/XBP1 axis upregulates the expression of Ufbp1 and ufmylation pathway genes in plasma cells, while Ufbp1 deficiency impairs ER expansion in plasma cells and retards immunoglobulin production. Structure and function analysis suggests that lysine 267 of Ufbp1, the main lysine in Ufbp1 that undergoes ufmylation, is dispensable for the development of plasmablasts, but is required for immunoglobulin production and stimulation of ER expansion in IRE1α-deficient plasmablasts. Thus, Ufbp1 distinctly regulates different branches of UPR pathway to promote plasma cell development and function. |
format | Online Article Text |
id | pubmed-6403283 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-64032832019-03-08 Ufbp1 promotes plasma cell development and ER expansion by modulating distinct branches of UPR Zhu, Huabin Bhatt, Brinda Sivaprakasam, Sathish Cai, Yafei Liu, Siyang Kodeboyina, Sai Karthik Patel, Nikhil Savage, Natasha M. Sharma, Ashok Kaufman, Randal J. Li, Honglin Singh, Nagendra Nat Commun Article The IRE1α/XBP1 branch of unfolded protein response (UPR) pathway has a critical function in endoplasmic reticulum (ER) expansion in plasma cells via unknown mechanisms; interestingly, another UPR branch, PERK, is suppressed during plasma cell development. Here we show that Ufbp1, a target and cofactor of the ufmylation pathway, promotes plasma cell development by suppressing the activation of PERK. By contrast, the IRE1α/XBP1 axis upregulates the expression of Ufbp1 and ufmylation pathway genes in plasma cells, while Ufbp1 deficiency impairs ER expansion in plasma cells and retards immunoglobulin production. Structure and function analysis suggests that lysine 267 of Ufbp1, the main lysine in Ufbp1 that undergoes ufmylation, is dispensable for the development of plasmablasts, but is required for immunoglobulin production and stimulation of ER expansion in IRE1α-deficient plasmablasts. Thus, Ufbp1 distinctly regulates different branches of UPR pathway to promote plasma cell development and function. Nature Publishing Group UK 2019-03-06 /pmc/articles/PMC6403283/ /pubmed/30842412 http://dx.doi.org/10.1038/s41467-019-08908-5 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Zhu, Huabin Bhatt, Brinda Sivaprakasam, Sathish Cai, Yafei Liu, Siyang Kodeboyina, Sai Karthik Patel, Nikhil Savage, Natasha M. Sharma, Ashok Kaufman, Randal J. Li, Honglin Singh, Nagendra Ufbp1 promotes plasma cell development and ER expansion by modulating distinct branches of UPR |
title | Ufbp1 promotes plasma cell development and ER expansion by modulating distinct branches of UPR |
title_full | Ufbp1 promotes plasma cell development and ER expansion by modulating distinct branches of UPR |
title_fullStr | Ufbp1 promotes plasma cell development and ER expansion by modulating distinct branches of UPR |
title_full_unstemmed | Ufbp1 promotes plasma cell development and ER expansion by modulating distinct branches of UPR |
title_short | Ufbp1 promotes plasma cell development and ER expansion by modulating distinct branches of UPR |
title_sort | ufbp1 promotes plasma cell development and er expansion by modulating distinct branches of upr |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403283/ https://www.ncbi.nlm.nih.gov/pubmed/30842412 http://dx.doi.org/10.1038/s41467-019-08908-5 |
work_keys_str_mv | AT zhuhuabin ufbp1promotesplasmacelldevelopmentanderexpansionbymodulatingdistinctbranchesofupr AT bhattbrinda ufbp1promotesplasmacelldevelopmentanderexpansionbymodulatingdistinctbranchesofupr AT sivaprakasamsathish ufbp1promotesplasmacelldevelopmentanderexpansionbymodulatingdistinctbranchesofupr AT caiyafei ufbp1promotesplasmacelldevelopmentanderexpansionbymodulatingdistinctbranchesofupr AT liusiyang ufbp1promotesplasmacelldevelopmentanderexpansionbymodulatingdistinctbranchesofupr AT kodeboyinasaikarthik ufbp1promotesplasmacelldevelopmentanderexpansionbymodulatingdistinctbranchesofupr AT patelnikhil ufbp1promotesplasmacelldevelopmentanderexpansionbymodulatingdistinctbranchesofupr AT savagenatasham ufbp1promotesplasmacelldevelopmentanderexpansionbymodulatingdistinctbranchesofupr AT sharmaashok ufbp1promotesplasmacelldevelopmentanderexpansionbymodulatingdistinctbranchesofupr AT kaufmanrandalj ufbp1promotesplasmacelldevelopmentanderexpansionbymodulatingdistinctbranchesofupr AT lihonglin ufbp1promotesplasmacelldevelopmentanderexpansionbymodulatingdistinctbranchesofupr AT singhnagendra ufbp1promotesplasmacelldevelopmentanderexpansionbymodulatingdistinctbranchesofupr |