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

Author

Listed:
  • Huabin Zhu

    (Augusta University)

  • Brinda Bhatt

    (Augusta University)

  • Sathish Sivaprakasam

    (Augusta University
    Texas Tech University Health Sciences Center)

  • 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
    Augusta University)

  • Nagendra Singh

    (Augusta University
    Augusta University)

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.

Suggested Citation

  • 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 & Nagendra Singh, 2019. "Ufbp1 promotes plasma cell development and ER expansion by modulating distinct branches of UPR," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08908-5
    DOI: 10.1038/s41467-019-08908-5
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    Cited by:

    1. Ryosuke Ishimura & Afnan H. El-Gowily & Daisuke Noshiro & Satoko Komatsu-Hirota & Yasuko Ono & Mayumi Shindo & Tomohisa Hatta & Manabu Abe & Takefumi Uemura & Hyeon-Cheol Lee-Okada & Tarek M. Mohamed , 2022. "The UFM1 system regulates ER-phagy through the ufmylation of CYB5R3," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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