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

• DOI: 10.1016/j.bbrc.2021.06.093
• Publication Date: 2021-07-23T11:12:05Z
• Authors: Kohei Kawaguchi; Miki Yamamoto-Hino; Satoshi Goto
• Keywords: 0303 health sciences; 03 medical and health sciences; HEK293 Cells; Surface Properties; Aspartic Acid Endopeptidases; Down-Regulation; Humans; Cells, Cultured; Glycosphingolipids

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.