Nature communications, 2019-03, Vol.10 (1), p.1084-1084, Article 1084
2019
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Details
- Autor(en) / Beteiligte
- Titel
- Ufbp1 promotes plasma cell development and ER expansion by modulating distinct branches of UPR
- Ist Teil von
- Nature communications, 2019-03, Vol.10 (1), p.1084-1084, Article 1084
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2019
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-019-08908-5Titel-ID: cdi_doaj_primary_oai_doaj_org_article_9adc16d000c24247b9a8853f22437942
- Format
- –
- Schlagworte
- Adaptor Proteins, Signal Transducing - genetics, Adaptor Proteins, Signal Transducing - isolation & purification, Adaptor Proteins, Signal Transducing - metabolism, Animals, Carrier Proteins - physiology, Cell Differentiation, Cell Line, eIF-2 Kinase - metabolism, Endoplasmic reticulum, Endoplasmic Reticulum - metabolism, Endoribonucleases - metabolism, Expansion, Female, Function analysis, Gene expression, Immunity, Humoral - physiology, Immunoglobulins, Lysine, Lysine - genetics, Male, Mice, Mice, Inbred C57BL, Mutation, Plasma, Plasma cells, Plasma Cells - physiology, Primary Cell Culture, Protein folding, Protein-Serine-Threonine Kinases - metabolism, Proteins, Recombinant Proteins - genetics, Recombinant Proteins - isolation & purification, Recombinant Proteins - metabolism, Structure-function relationships, Unfolded Protein Response - physiology, Up-Regulation, X-Box Binding Protein 1 - genetics, X-Box Binding Protein 1 - isolation & purification, X-Box Binding Protein 1 - metabolism