GlcCer Synthase (UDP-Glucose:Ceramide Glucosyltransferase, UGCG)

Abstract

Glycosphingolipids (GSLs) occur in vertebrates and lower animals, as well as in plants. They have been regarded as an enigmatic class of membrane lipids. Recent progress in biomembrane research indicates the existence of GSL microdomains (or “rafts”) in cell surface membranes (Simon and Ikonen 1997) GSLs form microdomains by a clustering of cholesterol and glycosyl-phosphatidyl inositol (GPI)-anchored proteins. The microdomains are thought to involve a variety of biological events such as cell signaling and cell-cell interaction. Another characteristic feature of GSLs is their chemical diversity: over 400 GSLs with different sugar chain structures have been isolated and determined. The structural studies to date indicate that almost all GSLs are derived from the simplest GSL, glucosylceramide. This is synthesized by a ceramidespecific β-glucosyltransferase (GlcT-I). Recent success in the molecular cloning of the gene encoding GlcT-I has provided new insights into the previously unrecognized roles of GSLs (Ichikawa et al. 1996). When the GlcT-I function is knocked out in mice by gene-targeting technology, the mouse dies at embryonic day 8 (Yamashita et al. 1999). This study clearly shows that GlcT-I plays an essential role during embryonic development and differentiation.