UDP-glucose: Ceramide glucosyltransferase (UGCG)

Glycosphingolipids (GSLs) occur in most of all cell membranes of vertebrates and lower animals, as well as in plants. They are major component in lipid microdomains or lipid rafts to play important roles in a wide range of physiological and pathophysiological processes. Glucosylceramide (GlcCer) is a key precursor lipid for the synthesis of over 400 GSLs with different sugar chain structures (Fig. 1.1). In addition, GlcCer has unexpected function as hexose donor for the synthesis of cholesterylglucoside (Akiyama et al. 2011). GlcCer formation in the Golgi/ER membranes is catalyzed by the enzyme ceramide glucosyltransferase (GlcT-1/GCS/CEGT/UGCG). Since catalytic activity is detectable when mammalian GlcT-1 protein is expressed in E. coli, suggesting no requirement of protein co-factor for the expression of its activity (Ichikawa et al. 1996). The gene encoding GlcT-1 is highly conserved, and the knockout animals of the GlcT-1 gene proved essential roles in embryo development (Yamashita et al. 1999; Kohyama-Koganeya et al. 2004). However, little is known about why the knockout mouse dies at embryonic day 8 and how GlcT-1 activity is regulated.