Abstract
Gangliosides are sialic-acid-containing glycosphingolipids expressed on all vertebrate cells. They are primarily positioned in the plasma membrane with the ceramide part anchored in the membrane and the glycan part exposed on the surface of the cell. These lipids have highly diverse structures, not the least with respect to their carbohydrate chains, with N-acetylneuraminic acid (NeuAc) and N-glycolylneuraminic acid (NeuGc) being the two most common sialic-acid residues in mammalian cells. Generally, human healthy tissue is deficient in NeuGc, but this molecule is expressed in tumors and in human fetal tissues, and was hence classified as an onco-fetal antigen. Gangliosides perform important functions through carbohydrate-specific interactions with proteins, for example, as receptors in cell–cell recognition, which can be exploited by viruses and other pathogens, and also by regulating signaling proteins, such as the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor receptor (VEGFR), through lateral interaction in the membrane. Through both mechanisms, tumor-associated gangliosides may affect malignant progression, which makes them attractive targets for cancer immunotherapies. In this review, we describe how proteins recognize gangliosides, focusing on the molecular recognition of gangliosides associated with cancer immunotherapy, and discuss the importance of these molecules in cancer research.
Highlights
Few lipid species included in biological membranes have received as much attention as glycosphingolipids (GSLs), and especially gangliosides, sialic-acid-containing GSLs
They were discovered by Ernst Klenk in the 1940s, who proposed the term “ganglioside” due to the abundance of these molecules in “Ganglionzellen”
The ceramide anchor is linked to a hydrophilic glycan head group, which is characterized by the presence of one or more sialic-acid residues; there is large variability of this structure
Summary
Few lipid species included in biological membranes have received as much attention as glycosphingolipids (GSLs), and especially gangliosides, sialic-acid-containing GSLs. The lipid anchor in sphingolipids builds on the long-chain amino alcohol sphingosine, which is coupled via its amino group to a fatty acid to form ceramide (Figure 1). The ceramide anchor is linked to a hydrophilic glycan head group, which is characterized by the presence of one or more sialic-acid residues (carbohydrates with a nine-carbon backbone and a carboxylic acid group); there is large variability of this structure. Positioned in the plasma membrane, gangliosides interact with other lipids and proteins, both laterally in the membrane and via their head groups, acting as cellular receptors that can be recognized by antibodies and other ganglioside-binding molecules. GANGLIOSIDES – GENERAL ARCHITECTURE, CELLULAR LOCALIZATION, AND BIOSYNTHESIS Gangliosides consist of a lipid anchor, the ceramide, decorated by a glycan head group of various complexity. Some indications relate their transcription to complex developmental and tissue-specific regulation, very www.frontiersin.org
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