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, Dmitry E. 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 journalArticlepeer-review

20 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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