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

SH Yim, RA Everley, FA Schildberg, SG Lee, A Orsi, ZR Barbati, K Karatepe, DE Fomenko, PA Tsuji, HR Luo, SP Gygi, R Sitia, AH Sharpe, DL Hatfield, VN Gladyshev

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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. © 2018 The Author(s)
Original languageEnglish
Pages (from-to)1387-1398
Number of pages12
JournalCell Reports
Volume23
Issue number5
DOIs
Publication statusPublished - 2018

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    Yim, SH., Everley, RA., Schildberg, FA., Lee, SG., Orsi, A., Barbati, ZR., Karatepe, K., Fomenko, DE., 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, 23(5), 1387-1398. https://doi.org/10.1016/j.celrep.2018.04.009