globoseries GSLs3). The biosynthesis of neutral GSLs and charged gangliosides requires the coordinated action of multiple sequentially acting glucosyltransferases and the availability of nucleotide sugar donors1). Most GSLs function primarily at the plasma membrane and undergo multiple rounds of recycling through the Golgi apparatus, where their glycans can be remodelled. Periodically, cell surface GSLs are endocytosed and progress through the endocytic system reaching late endosomes/lysosomes where they are sequentially degraded by acid glycohydrolases. GM3 and GM2 synthases function in the pathway as a sialyl transferase (ST3GAL5) and a GalNAc transferase (B4GALNT1) respectively.Gangliosides are sialic acid containing glycosphingolipids (GSLs) that are expressed at high levels in the nervous system of all vertebrates. Their functional roles are diverse, but still remain incompletely understood 1). However, we do have a good understanding of their biosynthesis that occurs in the Golgi apparatus starting with the transfer of glucose to ceramide on the cytosolic face of the membrane2). The GlcCer that is formed has two potential fates, it can progress through the Golgi apparatus via vesicular transport to form higher order GSLs including gangliosides, or it can move from the cis to the trans Golgi via the action of the transport protein FAPP2 to form the neutral Figure 1. Scheme of GSL biosynthesis showing the sugar headgroups which are attached to ceramide to generate unique and complex structures106Ganglioside biosynthetic diseasesFrances Platt1David Priestman, 2Emma Baple, 2Andrew Crosby and 1Prof Frances Platt1Department of Pharmacology, University of Oxford, UK, 2University of Exeter Medical school, Exeter, UK
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