N-ACETYLGLUCOSAMINYLTRANSFERASE REGULATES THE EXPRESSION OF NEOLACTOGLYCOLIPIDS INCLUDING SULFOGLUCURONYLGLYCOLIPIDS IN THE DEVELOPING NERVOUS-SYSTEM

Lactosylceramide N-acetylglucosaminyltransferase (GlcNAc-Tr) in the sy nthesis of lactotriosylceramide (LcOse3Cer) was characterized in the n ervous system. The microsomal membrane GlcNAc-Tr required a divalent m etal ion, preferably Mn2+, and a nonionic detergent. The pH optimum wa s around 7.0. The enzyme also transferred GlcNAc to neoactotetraosylce ramide (nLcOse4Cer), G(M1), and asialo-G(M1), but not to other glycoli pids. The K(m) value for lactosylceramide was 21 muM (V(max) = 91 pmol /mg/h), and that for nLcOse4Cer was 35 muM (V(max) = 112 pmol/mg/h). T he GlcNAc-Tr for the glycolipids appears to be separate from that for oligosaccharides. The developmental expression of GlcNAc-Tr, both in t he cerebral cortex and cerebellum, correlated well with the tissue lev els of LcOse3Cer, nLcOse4Cer, sulfoglucuronylglycolipids (SGGLs), and other neolacto series glycolipids (nLSGs). In the cerebral cortex, the specific activity of GlcNAc-Tr decreased sharply from a maximum level at embryonic day 15, and by postnatal day 10 onward, it was undetecta ble. In the adult cerebral cortex, although significant activities of other glycosyltransferases involved in the subsequent steps of the syn thesis of SGGLs were present, the absence of GlcNAc-Tr stymied the for mation of LcOse3Cer and therefore the synthesis of nLSGs, including SG GLs. In the cerebellum, the GlcNAc-Tr specific activity declined from the day of birth to postnatal day 3, but later, the activity increased and reached a maximum at postnatal day 15, which correlated with the increasing synthesis of nLSGs. The results indicate that lactosylceram ide GlcNAc-Tr is the key regulatory enzyme controlling the differentia l expression of all nLSGs in the developing nervous system.