biostudies-literatureLebreton SAssociazione Italiana per la Ricerca sul CancroTelethonAgence Nationale de la RechercheFondation pour la Recherche Médicalee2014709118https://www.ebi.ac.uk/biostudies/studies/S-EPMC8379914biostudies-literatureUnknown118(33)Glycosylphosphatidylinositol-anchored proteins (GPI-APs) are lipid-associated luminal secretory cargoes selectively sorted to the apical surface of the epithelia where they reside and play diverse vital functions. Cholesterol-dependent clustering of GPI-APs in the Golgi is the key step driving their apical sorting and their further plasma membrane organization and activity; however, the specific machinery involved in this Golgi event is still poorly understood. In this study, we show that the formation of GPI-AP homoclusters (made of single GPI-AP species) in the Golgi relies directly on the levels of calcium within cisternae. We further demonstrate that the TGN calcium/manganese pump, SPCA1, which regulates the calcium concentration within the Golgi, and Cab45, a calcium-binding luminal GProceedings of the National Academy of Sciences of the United States of AmericaCalcium levels in the Golgi complex regulate clustering and apical sorting of GPI-APs in polarized epithelial cells.PMC8379914IG-14442GGP15219/BANR-16-CE16-0019-01GGP15219DEQ20140329557Nitti MPaladino SPinton Pvon Blume JLiu DLebreton SZurzolo CfalseCalcium levels in the Golgi complex regulate clustering and apical sorting of GPI-APs in polarized epithelial cells.Glycosylphosphatidylinositol-anchored proteins (GPI-APs) are lipid-associated luminal secretory cargoes selectively sorted to the apical surface of the epithelia where they reside and play diverse vital functions. Cholesterol-dependent clustering of GPI-APs in the Golgi is the key step driving their apical sorting and their further plasma membrane organization and activity; however, the specific machinery involved in this Golgi event is still poorly understood. In this study, we show that the formation of GPI-AP homoclusters (made of single GPI-AP species) in the Golgi relies directly on the levels of calcium within cisternae. We further demonstrate that the TGN calcium/manganese pump, SPCA1, which regulates the calcium concentration within the Golgi, and Cab45, a calcium-binding luminal G2021-01-01T00:00:00Z2021 Aug2025-04-05T14:05:41.812Z2025-04-05T14:05:41.812ZS-EPMC83799143438966510.1073/pnas.2014709118