title: Simplifying complexity: genetically resculpting glycosphingolipid synthesis pathways in mice to reveal function.
abstract: Glycosphingolipids (GSLs) are a group of plasma-membrane lipids notable for their extremely diverse glycan head groups. The metabolic pathways for GSLs, including the identity of the biosynthetic enzymes needed for synthesis of their glycans, are now well understood. Many of their cellular functions, which include plasma-membrane organization, regulation of cell signaling, endocytosis, and serving as binding sites for pathogens and endogenous receptors, have also been established. However, an understanding of their functions in vivo had been lagging. Studies employing genetic manipulations of the GSL synthesis pathways in mice have been used to systematically reduce the large numbers and complexity of GSL glycan structures, allowing the in vivo functions of GSLs to be revealed from analysis of the resulting phenotypes. Findings from these studies have produced a clearer picture of the role of GSLs in mammalian physiology, which is the topic of this review.
authors.affiliation: Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 10, Room 9D-06; 10 Center DR MSC 1821, Bethesda, MD, 20892-1821, USA.
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Allende
authors.forename: Richard L
authors.initials: RL
authors.lastname: Proia
mesh_terms: D000818:Animals; D053898:Biosynthetic Pathways / Q000235:genetics*; D020895:Enterocytes / Q000166:cytology / Q000378:metabolism; D005700:Galactosyltransferases / Q000172:deficiency / Q000235:genetics*; D005786:Gene Expression Regulation; D006028:Glycosphingolipids / Q000096:biosynthesis* / Q000737:chemistry; D008099:Liver / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009420:Nervous System / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D006028:Glycosphingolipids; D005700:Galactosyltransferases