Biosynthesis and biological function of sulfoglycolipids

Abstract

Sulfation confers negative charge on glycolipids and the attached sulfate group presents a part of determinants for the molecular interactions. Mammalian sulfoglycolipids are comprised of two major members, sulfatide (SO3-3Gal-ceramide) and seminolipid (SO3-3Gal-alkylacylglycerol). Sulfatide is abundant in the myelin sheath and seminolipid is unique to the spermatogenic cells. The carbohydrate moiety of sulfatide and seminolipid is biosynthesized via sequential reactions catalyzed by common enzymes: ceramide galactosyltransferase (CGT) and cerebroside sulfotransferase (CST). To elucidate the biological function of sulfoglycolipids, we have purified CST, cloned the CST gene, and generated CST-knockout mice. CST-null mice completely lack sulfoglycolipids all over the body. CST-null mice manifest some neurological disorders due to myelin dysfunction, an aberrant enhancement of oligodendrocyte terminal differentiation, and an arrest of spermatogenesis. CST-deficiency ameliorates L-selectin-dependent monocyte infiltration in the renal interstitial inflammation, indicating that sulfatide is an endogenous ligand of L-selectin. Studies on the molecular mechanisms underlying the biological events for which sulfoglycolipids are essential are ongoing

Figure 1.

Structure of sulfatide and seminolipid.

Figure 2.

Biosythetic pathway of sulfatide and seminolipid.

Figure 3.

Organization of nodes of Ranvier and its alterations in CST-deficient mice. In wild-type mice (left side), myelin membranes and axon membranes form junctions at the paranode region and Na⁺ and K⁺ channels cluster at the node and juxtaparanode regions, respectively, separated by the septate-like axo-glial junction. In CST-deficient mice (right side), formation of the axo-glial junction is disordered and the clustering of Na⁺ and K⁺ channels is also disturbed.

Figure 4.

Lactate is the main energy source for male germ cells. The basal side of the blood testis barrier (interstitial compartment) is connected to blood and contains glucose, but the apical side (adluminal compartment) lacks glucose. Energy fuel is obtained in a form of lactate that is made from glucose in Sertoli cell. The release and uptake of lactate are mediated by monocarboxylate transporters (MCTs). GLUT, glucose transporter.