Signal peptide peptidase (SPP)- and SPP-like 3 (SPPL3)-dependent shedding of α1,6-fucosyltransferase (FUT8) differentially affects core fucosylation

Alpha1,6-fucosyltransferase (FUT8) biosynthesizes core fucose on N-glycans, which plays essential roles in various biological processes, including immunity and development. Although FUT8 is a Golgi-resident type II membrane protein, it is also secreted by an unknown mechanism. Here, we demonstrate that signal peptide peptidase (SPP) and signal peptide peptidase-like 3 (SPPL3), members of an intramembrane protease family, both cleave FUT8 for secretion.