Ufbp1 promotes plasma cell development and ER expansion by modulating distinct branches of UPR

Huabin Zhu, Brinda Bhatt, Sathish Sivaprakasam, Yafei Cai, Siyang Liu, Sai Karthik Kodeboyina, Nikhil Patel, Natasha M. Savage, Ashok Sharma, Randal J. Kaufman, Honglin Li and Nagendra Singh ()
Additional contact information
Huabin Zhu: Augusta University
Brinda Bhatt: Augusta University
Sathish Sivaprakasam: Augusta University
Yafei Cai: Nanjing Agricultural University
Siyang Liu: Augusta University
Sai Karthik Kodeboyina: Augusta University
Nikhil Patel: Augusta University
Natasha M. Savage: Augusta University
Ashok Sharma: Augusta University
Randal J. Kaufman: Sanford Burnham Prebys Medical Discovery Institute
Honglin Li: Augusta University
Nagendra Singh: Augusta University

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-08908-5

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