PT  - JOURNAL ARTICLE
AU  - Mizuki Ishida
AU  - Yuta Maki
AU  - Akinori Ninomiya
AU  - Yoko Takada
AU  - Philippe Campeau
AU  - Taroh Kinoshita
AU  - Yoshiko Murakami
TI  - Ethanolamine-phosphate on the second mannose is the preferential bridge for some of the brain GPI-anchored proteins
AID  - 10.1101/2020.11.26.399477
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2020.11.26.399477
4099  - http://biorxiv.org/content/early/2021/10/06/2020.11.26.399477.short
4100  - http://biorxiv.org/content/early/2021/10/06/2020.11.26.399477.full
AB  - Glycosylphosphatidylinositols (GPIs) are glycolipids that anchor many proteins (GPI-APs) on the cell surface. The core glycan of GPI precursor has three mannoses, which in mammals, are all modified by ethanolamine-phosphate (EthN-P). It is postulated that EthN-P on the third mannose (EthN-P-Man3) is the bridge between GPI to the protein and the second (EthN-P-Man2) is removed after GPI-protein attachment. However, EthN-P-Man2 may not be always transient, as mutations of PIGG, the enzyme that transfers EthN-P to Man2, result in inherited GPI deficiencies (IGDs), characterized by neuronal dysfunctions. Here, we show EthN-P on Man2 is the preferential bridge in some GPI-APs, among them, the ect-5’-nucleotidase and netrin G2. We found that CD59, a GPI-AP, is attached via EthN-P-Man2 both in PIGB-knockout cells, in which GPI lacks Man3 and with a small fraction, in wild type cells. Our findings modify the current view of GPI anchoring and provide mechanistic bases of IGDs caused by PIGG mutations.Competing Interest StatementThe authors have declared no competing interest.