SPPL3-dependent downregulation of the synthesis of (neo)lacto-series glycosphingolipid is required for the staining of cell surface CD59

Biochem Biophys Res Commun. 2021 Sep 24:571:81-87. doi: 10.1016/j.bbrc.2021.06.093. Epub 2021 Jul 23.

Abstract

CD59 is a small glycoprotein modified with a glycophosphatidylinositol (GPI) anchor that prevents the formation of the membrane attack complex, thereby protecting host cells from lysis. A previous study identified that cell surface CD59 staining required the intramembrane protease signal peptide peptidase-like 3 (SPPL3). However, the effect of SPPL3 on the staining of CD59 remains unknown. This study shows that SPPL3 is essential for the surface labeling of CD59 but not of major GPI-anchored proteins. Surface CD59 staining requires the intramembrane protease activity of SPPL3 and SPPL3-mediated suppression of the (neo)lacto-series glycosphingolipids (nsGSLs)-but not N-glycan-synthesis pathway. The abundance of nsGSLs may affect complement-dependent cytotoxicity by altering the abundance or accessibility of cell surface CD59.

Keywords: CD59; Complement system; GPI; SPPL3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspartic Acid Endopeptidases / metabolism*
  • Cells, Cultured
  • Down-Regulation*
  • Glycosphingolipids / biosynthesis*
  • Glycosphingolipids / chemistry
  • HEK293 Cells
  • Humans
  • Surface Properties

Substances

  • Glycosphingolipids
  • Aspartic Acid Endopeptidases