Lipid flippases ATP9A and ATP9B form a complex and contribute to the exocytic pathway from the Golgi

Type IV P-type ATPases (P4-ATPases) serve as lipid flippases, translocating membrane lipids from the exoplasmic (or luminal) leaflet to the cytoplasmic leaflet of lipid bilayers. In mammals, these P4-ATPases are localized to distinct subcellular compartments. ATP8A1 and ATP9A, members of the P4-ATPase family, are involved in endosome-mediated membrane trafficking, although the roles of P4-ATPases in the exocytic pathway remain to be clarified. ATP9A and ATP9B are located in the TGN, with ATP9A also present in endosomal compartments. This study revealed the overlapping roles of ATP9A and ATP9B in transporting VSVG from the Golgi to the plasma membrane within the exocytic pathway. Furthermore, we demonstrated that the flippase activities of ATP9A and ATP9B were crucial for the transport process. Notably, we discovered the formation of homomeric and/or heteromeric complexes between ATP9A and ATP9B. Therefore, ATP9A and ATP9B play a role in the exocytic pathway from the Golgi to the plasma membrane, forming either homomeric or heteromeric complexes.