Cell-specific in vivo functions of glycosphingolipids: lessons from genetic deletions of enzymes involved in glycosphingolipid synthesis
- PMID: 23473748
- DOI: 10.1016/j.plipres.2013.02.001
Cell-specific in vivo functions of glycosphingolipids: lessons from genetic deletions of enzymes involved in glycosphingolipid synthesis
Abstract
Glycosphingolipids (GSLs) are believed to be involved in many cellular events including trafficking, signaling and cellular interactions. Over the past decade considerable progress was made elucidating the function of GSLs by generating and exploring animal models with GSL-deficiency. Initial studies focused on exploring the role of complex sialic acid containing GSLs (gangliosides) in neuronal tissue. Although complex gangliosides were absent, surprisingly, the phenotype observed was rather mild. In subsequent studies, several mouse models with combinations of gene-deletions encoding GSL-synthesizing enzymes were developed. The results indicated that reduction of GSL-complexity correlated with severity of phenotypes. However, in these mice, accumulation of precursor GSLs or neobiosynthesized GSL-series seemed to partly compensate the loss of GSLs. Thus, UDP-glucose:ceramide glucosyltransferase (Ugcg), catalyzing the basic step of the glucosylceramide-based GSL-biosynthesis, was genetically disrupted. A total systemic deletion of Ugcg caused early embryonic lethality. Therefore, Ugcg was eliminated in a cell-specific manner using the cre/loxP-system. New insights into the cellular function of GSLs were gained. It was demonstrated that neurons require GSLs for differentiation and maintenance. In keratinocytes, preservation of the skin barrier depends on GSL synthesis and in enterocytes of the small intestine GSLs are involved in endocytosis and vesicular transport.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Similar articles
-
Hepatic glycosphingolipid deficiency and liver function in mice.Hepatology. 2010 May;51(5):1799-809. doi: 10.1002/hep.23545. Hepatology. 2010. PMID: 20432257
-
[Cell-specific deletion of glucosylceramide synthase in brain leads to severe neural defects after birth].Verh Dtsch Ges Pathol. 2006;90:193-202. Verh Dtsch Ges Pathol. 2006. PMID: 17867597 German.
-
Glycosphingolipid synthesis in cerebellar Purkinje neurons: roles in myelin formation and axonal homeostasis.Glia. 2010 Aug;58(10):1197-207. doi: 10.1002/glia.20999. Glia. 2010. PMID: 20544855
-
Glucosylceramide synthase and glycosphingolipid synthesis.Trends Cell Biol. 1998 May;8(5):198-202. doi: 10.1016/s0962-8924(98)01249-5. Trends Cell Biol. 1998. PMID: 9695839 Review.
-
Simplifying complexity: genetically resculpting glycosphingolipid synthesis pathways in mice to reveal function.Glycoconj J. 2014 Dec;31(9):613-22. doi: 10.1007/s10719-014-9563-5. Epub 2014 Oct 29. Glycoconj J. 2014. PMID: 25351657 Free PMC article. Review.
Cited by
-
Genetics of glycosylation in mammalian development and disease.Nat Rev Genet. 2024 May 9. doi: 10.1038/s41576-024-00725-x. Online ahead of print. Nat Rev Genet. 2024. PMID: 38724711 Review.
-
Metabolic Markers and Association of Biological Sex in Lupus Nephritis.Int J Mol Sci. 2023 Nov 18;24(22):16490. doi: 10.3390/ijms242216490. Int J Mol Sci. 2023. PMID: 38003679 Free PMC article.
-
Glycoconjugates: Synthesis, Functional Studies, and Therapeutic Developments.Chem Rev. 2022 Oct 26;122(20):15603-15671. doi: 10.1021/acs.chemrev.1c01032. Epub 2022 Sep 29. Chem Rev. 2022. PMID: 36174107 Free PMC article. Review.
-
Enterohemorrhagic Escherichia coli and a Fresh View on Shiga Toxin-Binding Glycosphingolipids of Primary Human Kidney and Colon Epithelial Cells and Their Toxin Susceptibility.Int J Mol Sci. 2022 Jun 21;23(13):6884. doi: 10.3390/ijms23136884. Int J Mol Sci. 2022. PMID: 35805890 Free PMC article. Review.
-
Primary Human Colon Epithelial Cells (pHCoEpiCs) Do Express the Shiga Toxin (Stx) Receptor Glycosphingolipids Gb3Cer and Gb4Cer and Are Largely Refractory but Not Resistant towards Stx.Int J Mol Sci. 2021 Sep 16;22(18):10002. doi: 10.3390/ijms221810002. Int J Mol Sci. 2021. PMID: 34576167 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous