TY - JOUR AU - Sandhoff, Roger AU - Sandhoff, Konrad TI - Emerging concepts of ganglioside metabolism. JO - FEBS letters VL - 592 IS - 23 SN - 1873-3468 CY - Chichester PB - Wiley M1 - DKFZ-2018-02349 SP - 3835 - 3864 PY - 2018 AB - Gangliosides (GGs) are sialic acid-containing glycosphingolipids (GSLs) and major membrane components enriched on cellular surfaces. Biosynthesis of mammalian GGs starts at the cytosolic leaflet of endoplasmic reticulum (ER) membranes with the formation of their hydrophobic ceramide anchors. After intracellular ceramide transfer to Golgi and trans-Golgi network (TGN) membranes, anabolism of GGs, as well as of other GSLs, is catalyzed by membrane-spanning glycosyltransferases (GTs) along the secretory pathway. Combined activity of only a few promiscuous GTs allows for the formation of cell-type-specific glycolipid patterns. Following an exocytotic vesicle flow to the cellular plasma membranes, GGs can be modified by metabolic reactions at or near the cellular surface. For degradation, GGs are endocytosed to reach late endosomes and lysosomes. Whereas membrane-spanning enzymes of the secretory pathway catalyze GSL and GG formation, a cooperation of soluble glycosidases, lipases and lipid-binding cofactors, namely the sphingolipid activator proteins (SAPs), act as the main players of GG and GSL catabolism at intralysosomal luminal vesicles (ILVs). LB - PUB:(DE-HGF)16 C6 - pmid:29802621 DO - DOI:10.1002/1873-3468.13114 UR - https://inrepo02.dkfz.de/record/142119 ER -