Figure 1.

Intracellular trafficking (in green circle) and function (in red triangle) of wild-type ABCA3 in an alveolar type II cell. After synthesis, immature ABCA3 is translocated in the ER (A) and then trafficked to the Golgi apparatus, where N-glycosylation takes place (B). After N-glycosylation, ABCA3 is routed via multivesicular bodies (MVBs) to the outer membrane of lamellar bodies (LBs), which are lysosome-related compartments (C) involved in LB biogenesis (E). When the lipoprotein in LBs is released via regulated exocytosis, ABCA3 stays in the plasma membrane and then is either recycled or degraded in lysosomes, undergoing proteolytic cleavage (D). PC from de novo synthesis (G) assembles into MVBs and LBs by the ABCA3 protein with ATPase activity (H) and then is released as a pulmonary surfactant component via exocytosis. Surfactant DPPC is also produced by the remodeling of PC from recycled surfactant liposomes (F). After remodeling, DPPC is taken up by the ABCA3 protein into MVBs and LBs, which are involved in surfactant metabolism.