Fig. 2.

Intracellular localization and transport of GlcCer and GalCer. In the “classical” model (shown in blue), GlcCer, synthesized on the cytosolic side of the cis-Golgi, is transported to the trans-Golgi and translocated to the luminal side, where synthesis of complex GSLs takes place. In the alternative model (shown in violet), ceramide is transported from the ER to the cytosol with the help of CERT (1), then GlcCer is synthesized on the cytosolic side of the trans-Golgi (2), from there most GlcCer is transported back to the cytoplasmic leaflet of ER with the help of the FAPP2 (3). There, GlcCer is translocated to the luminal side and transported again to the trans-Golgi apparatus, where complex GSLs are synthesized (4). Remaining GlcCer is transported by FAPP2 from the cytosolic surface of the trans-Golgi to the cytosolic surface of the plasma membrane (5). GalCer is synthesized on the luminal side of the ER (shown in red). From there, it is transported to the trans-Golgi compartment, where complex galactosphingolipids and sulfatides are synthesized. FAPP2—4-phosphate adaptor protein-2, CERT—ceramide transport protein.