Abstract
Glycosphingolipids (GSLs) are composed of hydrophobic ceramide and hydrophilic sugar chains. GSLs cluster to form membrane microdomains (lipid rafts) on plasma membranes, along with several kinds of transducer molecules, including Src family kinases and small G proteins. However, GSL-mediated biological functions remain unclear. Lactosylceramide (LacCer, CDw17) is highly expressed on the plasma membranes of human phagocytes and mediates several immunological and inflammatory reactions, including phagocytosis, chemotaxis, and superoxide generation. LacCer forms membrane microdomains with the Src family tyrosine kinase Lyn and the Gαi subunit of heterotrimeric G proteins. The very long fatty acids C24:0 and C24:1 are the main ceramide components of LacCer in neutrophil plasma membranes and are directly connected with the fatty acids of Lyn and Gαi. These observations suggest that the very long fatty acid chains of ceramide are critical for GSL-mediated outside-in signaling. Sphingosine is another component of ceramide, with the hydrolysis of ceramide by ceramidase producing sphingosine and fatty acids. Sphingosine is phosphorylated by sphingosine kinase to sphingosine-1-phosphate, which is involved in a wide range of cellular functions, including growth, differentiation, survival, chemotaxis, angiogenesis, and embryogenesis, in various types of cells. This review describes the role of ceramide moiety of GSLs and its metabolites in immunological and inflammatory reactions in human.
Highlights
Biological membranes are mainly composed of phospholipids, sphingolipids, cholesterol, and membrane-associated proteins
We recently showed that very long fatty acid chains of ceramide, such as C24:0 and C24:1, are responsible for the direct connection between lactosylceramide (LacCer, CDw17) and palmitoylated signal transducer molecules [5]
This review describes the role of the fatty acid chains of ceramide in GSL-mediated outside-in signaling in promoting GSL-enriched domain-mediated cellular functions, as well as the activities of S1P in inflammatory reactions of keratinocytes in human
Summary
Biological membranes are mainly composed of phospholipids, sphingolipids, cholesterol, and membrane-associated proteins. These molecules are nonhomogeneously distributed in membranes and can rearrange, leading to the formation of membrane “domains” with highly differentiated molecular compositions and supramolecular architectures, which are stabilized by lateral interactions among the membrane components. There is a general consensus on the roles played by the ceramide moiety of GSLs in promoting the formation and stabilization of membrane lipid domains. Ceramide was shown to be involved in GSL-mediated functions and several biological activities [3, 4]. This review describes the role of the fatty acid chains of ceramide in GSL-mediated outside-in signaling in promoting GSL-enriched domain-mediated cellular functions, as well as the activities of S1P in inflammatory reactions of keratinocytes in human
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