Role of Selenof as a Gatekeeper of Secreted Disulfide-Rich Glycoproteins

Sun Hee Yim, Robert A. Everley, Frank A. Schildberg, Sang Goo Lee, Andrea Orsi, Zachary R. Barbati, Kutay Karatepe, Dmitri Fomenko, Petra A. Tsuji, Hongbo R. Luo, Steven P. Gygi, Roberto Sitia, Arlene H. Sharpe, Dolph L. Hatfield, Vadim N. Gladyshev

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Selenof (15-kDa selenoprotein; Sep15) is an endoplasmic reticulum (ER)-resident thioredoxin-like oxidoreductase that occurs in a complex with UDP-glucose:glycoprotein glucosyltransferase. We found that Selenof deficiency in mice leads to elevated levels of non-functional circulating plasma immunoglobulins and increased secretion of IgM during in vitro splenic B cell differentiation. However, Selenof knockout animals show neither enhanced bacterial killing capacity nor antigen-induced systemic IgM activity, suggesting that excess immunoglobulins are not functional. In addition, ER-to-Golgi transport of a target glycoprotein was delayed in Selenof knockout embryonic fibroblasts, and proteomic analyses revealed that Selenof deficiency is primarily associated with antigen presentation and ER-to-Golgi transport. Together, the data suggest that Selenof functions as a gatekeeper of immunoglobulins and, likely, other client proteins that exit the ER, thereby supporting redox quality control of these proteins. Yim et al. report that Selenof (15-kDa selenoprotein; Sep15) functions as a gatekeeper of immunoglobulins and, likely, other client proteins en route from the ER to the Golgi apparatus, thereby preventing secretion of dysfunctional proteins and supporting redox quality control.

Original languageEnglish (US)
Pages (from-to)1387-1398
Number of pages12
JournalCell Reports
Volume23
Issue number5
DOIs
StatePublished - May 1 2018

Fingerprint

Endoplasmic Reticulum
Disulfides
Immunoglobulins
Glycoproteins
Selenoproteins
Quality control
Immunoglobulin M
Proteins
Quality Control
Oxidation-Reduction
Antigens
Thioredoxins
Fibroblasts
Antigen Presentation
Golgi Apparatus
Oxidoreductases
Animals
Proteomics
Cells
Cell Differentiation

Keywords

  • IgM
  • Selenof
  • Sep15
  • endoplasmic reticulum
  • gatekeeper
  • immunoglobulins
  • knockout mouse
  • oxidoreductase
  • selenoprotein

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Yim, S. H., Everley, R. A., Schildberg, F. A., Lee, S. G., Orsi, A., Barbati, Z. R., ... Gladyshev, V. N. (2018). Role of Selenof as a Gatekeeper of Secreted Disulfide-Rich Glycoproteins. Cell Reports, 23(5), 1387-1398. https://doi.org/10.1016/j.celrep.2018.04.009

Role of Selenof as a Gatekeeper of Secreted Disulfide-Rich Glycoproteins. / Yim, Sun Hee; Everley, Robert A.; Schildberg, Frank A.; Lee, Sang Goo; Orsi, Andrea; Barbati, Zachary R.; Karatepe, Kutay; Fomenko, Dmitri; Tsuji, Petra A.; Luo, Hongbo R.; Gygi, Steven P.; Sitia, Roberto; Sharpe, Arlene H.; Hatfield, Dolph L.; Gladyshev, Vadim N.

In: Cell Reports, Vol. 23, No. 5, 01.05.2018, p. 1387-1398.

Research output: Contribution to journalArticle

Yim, SH, Everley, RA, Schildberg, FA, Lee, SG, Orsi, A, Barbati, ZR, Karatepe, K, Fomenko, D, Tsuji, PA, Luo, HR, Gygi, SP, Sitia, R, Sharpe, AH, Hatfield, DL & Gladyshev, VN 2018, 'Role of Selenof as a Gatekeeper of Secreted Disulfide-Rich Glycoproteins', Cell Reports, vol. 23, no. 5, pp. 1387-1398. https://doi.org/10.1016/j.celrep.2018.04.009
Yim SH, Everley RA, Schildberg FA, Lee SG, Orsi A, Barbati ZR et al. Role of Selenof as a Gatekeeper of Secreted Disulfide-Rich Glycoproteins. Cell Reports. 2018 May 1;23(5):1387-1398. https://doi.org/10.1016/j.celrep.2018.04.009
Yim, Sun Hee ; Everley, Robert A. ; Schildberg, Frank A. ; Lee, Sang Goo ; Orsi, Andrea ; Barbati, Zachary R. ; Karatepe, Kutay ; Fomenko, Dmitri ; Tsuji, Petra A. ; Luo, Hongbo R. ; Gygi, Steven P. ; Sitia, Roberto ; Sharpe, Arlene H. ; Hatfield, Dolph L. ; Gladyshev, Vadim N. / Role of Selenof as a Gatekeeper of Secreted Disulfide-Rich Glycoproteins. In: Cell Reports. 2018 ; Vol. 23, No. 5. pp. 1387-1398.
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AU - Schildberg, Frank A.

AU - Lee, Sang Goo

AU - Orsi, Andrea

AU - Barbati, Zachary R.

AU - Karatepe, Kutay

AU - Fomenko, Dmitri

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AU - Luo, Hongbo R.

AU - Gygi, Steven P.

AU - Sitia, Roberto

AU - Sharpe, Arlene H.

AU - Hatfield, Dolph L.

AU - Gladyshev, Vadim N.

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