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

Cell Rep. 2018 May 1;23(5):1387-1398. doi: 10.1016/j.celrep.2018.04.009.


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.

Keywords: IgM; Selenof; Sep15; endoplasmic reticulum; gatekeeper; immunoglobulins; knockout mouse; oxidoreductase; selenoprotein.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • Cell Line
  • Endoplasmic Reticulum / genetics
  • Endoplasmic Reticulum / immunology*
  • Fibroblasts / cytology
  • Fibroblasts / immunology
  • Golgi Apparatus / genetics
  • Golgi Apparatus / immunology*
  • Immunoglobulin M / genetics
  • Immunoglobulin M / immunology*
  • Mice
  • Mice, Knockout
  • Selenoproteins / genetics
  • Selenoproteins / immunology*
  • Spleen / cytology
  • Spleen / immunology


  • Immunoglobulin M
  • Selenof protein, mouse
  • Selenoproteins