Biosynthesis of the major brain gangliosides GD1a and GT1b

Elizabeth R. Sturgill, Kazuhiro Aoki, Pablo H.H. Lopez, Daniel Colacurcio, Katarina Vajn, Ileana Lorenzini, Senka Majić, Won Ho Yang, Marija Heffer, Michael Tiemeyer, Jamey D. Marth, Ronald L. Schnaar

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Gangliosides-sialylated glycosphingolipids-are the major glycoconjugates of nerve cells. The same four structures-GM1, GD1a, GD1b and GT1b-comprise the great majority of gangliosides in mammalian brains. They share a common tetrasaccharide core (Gal1-3GalNAc1-4Gal1-4Glc1-1′Cer) with one or two sialic acids on the internal galactose and zero (GM1 and GD1b) or one (GD1a and GT1b) 2-3-linked sialic acid on the terminal galactose. Whereas the genes responsible for the sialylation of the internal galactose are known, those responsible for terminal sialylation have not been established in vivo. We report that St3gal2 and St3gal3 are responsible for nearly all the terminal sialylation of brain gangliosides in the mouse. When brain ganglioside expression was analyzed in adult St3gal1-, St3gal2-, St3gal3-and St3gal4-null mice, only St3gal2-null mice differed significantly from wild type, expressing half the normal amount of GD1a and GT1b. St3gal1/2-double-null mice were no different than St3gal2-single-null mice; however, St3gal2/3-double-null mice were >95 depleted in gangliosides GD1a and GT1b. Total ganglioside expression (lipid-bound sialic acid) in the brains of St3gal2/3-double-null mice was equivalent to that in wild-type mice, whereas total protein sialylation was reduced by half. St3gal2/3-double-null mice were small, weak and short lived. They were half the weight of wild-type mice at weaning and displayed early hindlimb dysreflexia. We conclude that the St3gal2 and St3gal3 gene products (ST3Gal-II and ST3Gal-III sialyltransferases) are largely responsible for ganglioside terminal 2-3 sialylation in the brain, synthesizing the major brain gangliosides GD1a and GT1b.

Original languageEnglish
Pages (from-to)1289-1301
Number of pages13
JournalGlycobiology
Volume22
Issue number10
DOIs
Publication statusPublished - 2012 Oct 1

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Gangliosides
Biosynthesis
Brain
beta-galactoside alpha-2,3-sialyltransferase
Galactose
N-Acetylneuraminic Acid
Genes
Sialyltransferases
Sialic Acids
Glycosphingolipids
Glycoconjugates
Neurons
GD1a ganglioside
trisialoganglioside GT1
Lipids
Hindlimb
Weaning
Proteins
Weights and Measures

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Sturgill, E. R., Aoki, K., Lopez, P. H. H., Colacurcio, D., Vajn, K., Lorenzini, I., ... Schnaar, R. L. (2012). Biosynthesis of the major brain gangliosides GD1a and GT1b. Glycobiology, 22(10), 1289-1301. https://doi.org/10.1093/glycob/cws103
Sturgill, Elizabeth R. ; Aoki, Kazuhiro ; Lopez, Pablo H.H. ; Colacurcio, Daniel ; Vajn, Katarina ; Lorenzini, Ileana ; Majić, Senka ; Yang, Won Ho ; Heffer, Marija ; Tiemeyer, Michael ; Marth, Jamey D. ; Schnaar, Ronald L. / Biosynthesis of the major brain gangliosides GD1a and GT1b. In: Glycobiology. 2012 ; Vol. 22, No. 10. pp. 1289-1301.
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Sturgill, ER, Aoki, K, Lopez, PHH, Colacurcio, D, Vajn, K, Lorenzini, I, Majić, S, Yang, WH, Heffer, M, Tiemeyer, M, Marth, JD & Schnaar, RL 2012, 'Biosynthesis of the major brain gangliosides GD1a and GT1b', Glycobiology, vol. 22, no. 10, pp. 1289-1301. https://doi.org/10.1093/glycob/cws103

Biosynthesis of the major brain gangliosides GD1a and GT1b. / Sturgill, Elizabeth R.; Aoki, Kazuhiro; Lopez, Pablo H.H.; Colacurcio, Daniel; Vajn, Katarina; Lorenzini, Ileana; Majić, Senka; Yang, Won Ho; Heffer, Marija; Tiemeyer, Michael; Marth, Jamey D.; Schnaar, Ronald L.

In: Glycobiology, Vol. 22, No. 10, 01.10.2012, p. 1289-1301.

Research output: Contribution to journalArticle

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AU - Lorenzini, Ileana

AU - Majić, Senka

AU - Yang, Won Ho

AU - Heffer, Marija

AU - Tiemeyer, Michael

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AU - Schnaar, Ronald L.

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N2 - Gangliosides-sialylated glycosphingolipids-are the major glycoconjugates of nerve cells. The same four structures-GM1, GD1a, GD1b and GT1b-comprise the great majority of gangliosides in mammalian brains. They share a common tetrasaccharide core (Gal1-3GalNAc1-4Gal1-4Glc1-1′Cer) with one or two sialic acids on the internal galactose and zero (GM1 and GD1b) or one (GD1a and GT1b) 2-3-linked sialic acid on the terminal galactose. Whereas the genes responsible for the sialylation of the internal galactose are known, those responsible for terminal sialylation have not been established in vivo. We report that St3gal2 and St3gal3 are responsible for nearly all the terminal sialylation of brain gangliosides in the mouse. When brain ganglioside expression was analyzed in adult St3gal1-, St3gal2-, St3gal3-and St3gal4-null mice, only St3gal2-null mice differed significantly from wild type, expressing half the normal amount of GD1a and GT1b. St3gal1/2-double-null mice were no different than St3gal2-single-null mice; however, St3gal2/3-double-null mice were >95 depleted in gangliosides GD1a and GT1b. Total ganglioside expression (lipid-bound sialic acid) in the brains of St3gal2/3-double-null mice was equivalent to that in wild-type mice, whereas total protein sialylation was reduced by half. St3gal2/3-double-null mice were small, weak and short lived. They were half the weight of wild-type mice at weaning and displayed early hindlimb dysreflexia. We conclude that the St3gal2 and St3gal3 gene products (ST3Gal-II and ST3Gal-III sialyltransferases) are largely responsible for ganglioside terminal 2-3 sialylation in the brain, synthesizing the major brain gangliosides GD1a and GT1b.

AB - Gangliosides-sialylated glycosphingolipids-are the major glycoconjugates of nerve cells. The same four structures-GM1, GD1a, GD1b and GT1b-comprise the great majority of gangliosides in mammalian brains. They share a common tetrasaccharide core (Gal1-3GalNAc1-4Gal1-4Glc1-1′Cer) with one or two sialic acids on the internal galactose and zero (GM1 and GD1b) or one (GD1a and GT1b) 2-3-linked sialic acid on the terminal galactose. Whereas the genes responsible for the sialylation of the internal galactose are known, those responsible for terminal sialylation have not been established in vivo. We report that St3gal2 and St3gal3 are responsible for nearly all the terminal sialylation of brain gangliosides in the mouse. When brain ganglioside expression was analyzed in adult St3gal1-, St3gal2-, St3gal3-and St3gal4-null mice, only St3gal2-null mice differed significantly from wild type, expressing half the normal amount of GD1a and GT1b. St3gal1/2-double-null mice were no different than St3gal2-single-null mice; however, St3gal2/3-double-null mice were >95 depleted in gangliosides GD1a and GT1b. Total ganglioside expression (lipid-bound sialic acid) in the brains of St3gal2/3-double-null mice was equivalent to that in wild-type mice, whereas total protein sialylation was reduced by half. St3gal2/3-double-null mice were small, weak and short lived. They were half the weight of wild-type mice at weaning and displayed early hindlimb dysreflexia. We conclude that the St3gal2 and St3gal3 gene products (ST3Gal-II and ST3Gal-III sialyltransferases) are largely responsible for ganglioside terminal 2-3 sialylation in the brain, synthesizing the major brain gangliosides GD1a and GT1b.

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Sturgill ER, Aoki K, Lopez PHH, Colacurcio D, Vajn K, Lorenzini I et al. Biosynthesis of the major brain gangliosides GD1a and GT1b. Glycobiology. 2012 Oct 1;22(10):1289-1301. https://doi.org/10.1093/glycob/cws103