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Review
. 2014 Dec;31(9):613-22.
doi: 10.1007/s10719-014-9563-5. Epub 2014 Oct 29.

Simplifying complexity: genetically resculpting glycosphingolipid synthesis pathways in mice to reveal function

Maria Laura Allende  1 , Richard L Proia
Affiliations
Review

Simplifying complexity: genetically resculpting glycosphingolipid synthesis pathways in mice to reveal function

Maria Laura Allende et al. Glycoconj J. 2014 Dec.

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.

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Figures

Fig. 1
Fig. 1
GSL synthesis pathways. Genes that have been targeted are in the rounded boxes. The major mouse phenotypes caused by genetic blocks in the GSL pathways are indicated in red text. For a description of the complete pathways, see Merrill [1]. Cer, ceramide; GalCer, galactosylceramide; GlcCer, glucosylceramide; LacCer, lactosylceramide; NeuNAc, neuraminic acid
Fig. 2
Fig. 2
In vivo GSL functions revealed by whole body and conditional gene deletion studies in mice
See this image and copyright information in PMC

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