Sulfatide Synthase

Abstract

Two major sulfoglycolipids exist in the mammal: one being the sulfatide, which is a sphingolipid and the other being the seminolipid, which is an ether glycerolipid. Sulfatide is a major lipid component of the myelin sheath and is synthesized in the myelin-generating cells, oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system. Seminolipid is synthesized in spermatocytes and maintained in the subsequent germ-cell stages. The carbohydrate moiety of sulfatide and seminolipid has the same structure and are biosynthesized via sequential reactions catalyzed by common enzymes: ceramide galactosyltransferase (CGT, EC 2.4.1.45) and cerebroside sulfotransferase (CST, EC 2.8.2.11) (Fig. 1). This sulfotransferase is also known as sulfatide synthase. CST catalyzes the transfer of sulfonate group from 3′-phosphoadenosine 5′-phosphosulfate (PAPS) to the C3 position of the non-reducing terminal galactose of glycolipid oligosaccharides. We purified CST homogeneously from human renal cancer cells (Honke et al. 1996) and subsequently isolated a cDNA clone of CST from a cDNA library of human renal cancer cells on the basis of the partial amino acid sequences of the purified enzyme (Honke et al. 1997). Furthermore, we cloned human genomic DNA (Tsuda et al. 2000) and mouse cDNA and genomic DNA (Hirahara et al. 2000). CST includes PAPS recognizing motifs as the other sulfotransferases do. CST possesses two N-glycans, and the C-terminal one is essential for its enzymatic activity. CST is expressed in a tissue-specific manner, and is highly expressed in brain, kidney, testis and alimentary system. This tissue-specific expression of the CST gene is regulated by the alternative usage of multiple promoters (Hirahara et al. 2000).