Remodeling of GPI-APs in mammalian cells and yeast. (A) Remodeling of mammalian GPI-APs. Biosynthesis of GPI is performed in the ER through an enzymatic reaction pathway consisting of 10 steps (Kinoshita et al., 2008; Fujita and Kinoshita, 2010). Preformed GPI is attached to the C-terminus of a newly synthesized protein by GPI transamidase (TA). The acyl chain linked to inositol is eliminated by PGAP1. A side-chain EtNP attached to the second mannose is removed by PGAP5. After arrival of GPI-APs at the Golgi, fatty acid remodeling occurs; an unsaturated acid at the sn-2 position in the GPI lipid is removed by PGAP3 and then a saturated fatty acid (stearic acid) is transferred back. PGAP2 is a noncatalytic protein involved in the latter reaction. The putative catalytic component of the acyltransferase (Acyl-T) has yet to be discovered. (B) Remodeling of GPI-APs in the yeast Saccharomyces cerevisiae. After attachment of GPI to proteins, the acyl chain linked to inositol is eliminated by Bst1p (PGAP1 homologue). Then, the fatty acid remodeling of the GPI anchor is performed in the ER, mediated by Per1p (PGAP3 homologue) and Gup1p. In yeast, the diacylglycerol moiety in many GPI-APs is exchanged with ceramide by Cwh43p. Ted1p and Cdc1p, homologues of mammalian PGAP5, are localized in the ER. It was reported that Ted1p acts together with Emp24p and Erv25p, and that Cdc1p functions after Per1p and Gup1p in the same pathway, which suggests that they are involved in GPI remodeling. Side-chain EtNPs on the first and second mannoses are required for ceramide remodeling, whereas it remains unclear whether the side-chain EtNPs are eliminated.