Sulfoglucuronyl Neolactoglycolipids in Adult Cerebellum: Specific Absence in Murine Mutants with Purkinje Cell Abnormality

Abstract

It is shown here that glycolipids of the sulfoglucuronyl neolacto series (SGGLs) are present in the adult rodent cerebellum. SGGLs were not detected in the cerebellar murine mutants lurcher, Purkinje cell degeneration, and staggerer, in which Purkinje cell loss is the primary defect. SGGLs were present, however, in normal amounts in weaver and reeler mutants, in which there is a major and relatively specific loss of granule cells without obvious deficiency in Purkinje cells. In the myelin-deficient quaking mutant, the expression of SGGLs also was nearly normal. The loss of SGGLs in Purkinje cell-deficient mutants was specific, since most of the major lipids were not affected significantly and only the percentage composition of other lipids, such as sulfatides and gangliosides, was altered in the mutants. These and other results strongly suggest that SGGLs and other glycolipids of the paragloboside family are localized specifically in Purkinje cells and their arbors in the adult cerebellum. This is the first demonstration of the localization of a specific glycolipid and its analogs in a specific cell type in the nervous system.

N-Acetylglucosaminyl Transferase Regulates the Expression of the Sulfoglucuronyl Glycolipids in Specific Cell Types in Cerebellum during Development

“…Other cell types do not have this enzyme activity. Deficiency of GlcNAc-Tr in the Purkinje cell abnormality mutants would explain severe reduction of all neolactoglycolipids derived from LcOse 3 Cer in the mutants (1,(27)(28)(29). Although levels of LcOse 3 Cer were not measured in the mutants' cerebella, analysis of its immediate product nLcOse 4 Cer showed that it was only 4, Ͻ1, and 2.6% of the normal (ϳ3 ng/mg dry weight) in Lc/ϩ, tg la /tg la , and pcd/pcd mutants, respectively (27,29).…”

“…The loss of SGGLs and other glycolipids derived from LcOse 3 Cer such as, lactoneotetraosylceramide, lactoneohexaosylceramide, Le x antigens, and ganglioside nLD1, in these mutants was specific, since other lipids were not affected significantly. The expression of SGGLs was essentially normal in other cerebellar mutants, such as weaver, reeler, and quaking, where cells other than Purkinje cells are primarily affected (27)(28)(29).…”

“…Mutant mice were reared in our animal colony (27)(28)(29). Radioactive sugar nucleotides were purchased from DuPont NEN.…”

“…Previously we have shown that SGGLs were undetectable in the cerebella of murine mutants, such as Purkinje cell degeneration (pcd/pcd), lurcher (Lc/ϩ), and staggerer (sg/ sg), where Purkinje cell loss is the primary defect (27)(28)(29). In nervous mutant (nr/nr) where Purkinje cell loss is not as severe or in leaner (tg la /tg la ) where selective degeneration of Purkinje cells occurs, the loss of SGGLs was also limited (27)(28)(29). The loss of SGGLs and other glycolipids derived from LcOse 3 Cer such as, lactoneotetraosylceramide, lactoneohexaosylceramide, Le x antigens, and ganglioside nLD1, in these mutants was specific, since other lipids were not affected significantly.…”

Molecular Cloning and Characterization of UDP-GlcNAc:Lactosylceramide β1,3-N-Acetylglucosaminyltransferase (β3Gn-T5), an Essential Enzyme for the Expression of HNK-1 and Lewis X Epitopes on Glycolipids

“…In the adult rat cerebellum, the expression of SGGLs is kept constant (16,17). Immunohistochemical studies localized SGGLs in specific cells during the development of the cerebellum, and suggested some biological functions for neuron guidance (14,15,17,18). In rat cerebral cortex, the expression of SGGLs peaked at embryonic day (ED) 19 and then decreased until postnatal PD 5, and had almost completely disappeared by PD 20. Carbohydrate chains on SGGLs are extended by stepwise reactions catalyzed by glycosyltransferases.…”