Studies on the Biosynthesis of Gangliosides

Kaufman, Bernard; Basu, Subhash; Roseman, Saul

doi:10.1016/b978-1-4831-9855-2.50017-4

Cited by 50 publications

(26 citation statements)

References 18 publications

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“…Almost all mammalian tis- 2 We propose here to assign the name of ST3Gal V to GM3 synthase. HL60 leukemia cells (37).…”

Section: Resultsmentioning

confidence: 99%

“…Among sialyl-transferase cDNAs, ST3Gal III (ST3N) (Gal␤1,3/1,4GlcNAc ␣2,3S-T showed the highest homology. 2 The second group is ST3Gal III (Gal␤1,3GalNAc/Gal␤1,4GlcNAc ␣2,3S-T). The next groups are ST3Gal IA (ST3O) (Gal␤1,3GalNAc ␣2,3S-T) and ST3Gal II (ST3GalA2) (Gal␤1,3GalNAc␣ 2,3S-T).…”

Section: Resultsmentioning

confidence: 99%

“…Gangliosides are acidic, sialic acid-containing glycosphingolipids and are ubiquitously expressed in all tissues and cells (1,2). Their carbohydrate structures are strictly regulated, depending on the development of tissues, differentiation, and malignant transformation of cells (3,4).…”

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confidence: 99%

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Expression Cloning of Mouse cDNA of CMP-NeuAc:Lactosylceramide α2,3-Sialyltransferase, an Enzyme That Initiates the Synthesis of Gangliosides

Fukumoto

Miyazaki

Goto

et al. 1999

Journal of Biological Chemistry

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Expression cloning of a cDNA for the ␣2,3-sialyltransferase (GM3 synthase) (EC 2.4.99.-) gene was performed using a GM3-lacking mouse fibroblast line L cell and anti-GM3 monoclonal antibody. Plasmids from a cDNA library generated with poly(A) ؉ RNA of a mouse fibrosarcoma line CMS5j and pdl3027 (polyoma T antigen) were co-transfected into L cells. The isolated cDNA clone pM3T-7 predicted a type II membrane protein with 13 amino acids of cytoplasmic domain, 17 amino acids of transmembrane region, and a large catalytic domain with 329 amino acids. Introduction of the cDNA clone into L cells resulted in the neo-synthesis of GM3 and high activity of ␣2,3-sialyltransferase. Among glycosphingolipids, only lactosylceramide showed significant activity as an acceptor, indicating that this gene product is a sialyltransferase specific for the synthesis of GM3. An amino acid sequence deduced from the cloned cDNA showed the typical sialyl motif with common features among ␣2,3-sialyltransferases. Among various mouse tissues, brain, liver, and testis showed relatively high expression of a 2.3-kilobase mRNA, whereas all tissues, more or less, expressed this gene.

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“…Almost all mammalian tis- 2 We propose here to assign the name of ST3Gal V to GM3 synthase. HL60 leukemia cells (37).…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Expression Cloning of Mouse cDNA of CMP-NeuAc:Lactosylceramide α2,3-Sialyltransferase, an Enzyme That Initiates the Synthesis of Gangliosides

Fukumoto

Miyazaki

Goto

et al. 1999

Journal of Biological Chemistry

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“…Gangliosides are synthesized by consecutive addition of monosaccharides to ceramide by multiple glycosyltransferases in the Golgi apparatus (6)(7)(8) and are then transferred to the outer leaflet of the plasma membrane. Among the many glycosyltransferases, (31,4 GalNActransferase ((31,4 GalNAc-T; GM2/GD2 synthase; EC 2.4.1.92) plays an important role in biosynthesis of almost all complex gangliosides ( Fig.…”

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confidence: 99%

Mice with disrupted GM2/GD2 synthase gene lack complex gangliosides but exhibit only subtle defects in their nervous system.

Takamiya

Yamamoto

Furukawa

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

354

285

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“…The ST8Sia I gene has been cloned from human [15,16,17], mouse [18], and rat [19] and consists of 5 exons that show high similarity among the species [2]. Analysis of all cloned enzymes showed that ST8Sia I catalyzes the formation of GD3 [14,20,21] and LD1 [20] and thus is a GD3 synthase (ST-II). However, Nara et al [22] reported that this enzyme utilizes gangliosides GM1b, GD1a, and GT1b as exogenous substrates, in addition to GM3, indicating this enzyme catalyzes the formation of not only GD3, but also GD1c, GT1a, and GQ1b in vitro.…”

Section: Sialyltransferase Families (Ec 2499y)mentioning

confidence: 99%

Cloning and Transcriptional Regulation of Genes Responsible for Synthesis of Gangliosides

Zeng¹,

2008

CDT

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Ganglioside synthases are glycosyltransferases involved in the biosynthesis of glycoconjugates. A number of ganglioside synthase genes have been cloned and characterized. They are classified into different families of glycosyltransferases based on similarities of their amino acid sequences. Tissue-specific expression of these genes has been analyzed by hybridization using cDNA fragments. Enzymatic characterization with the expressed recombinant enzymes showed these enzymes differ in their donor and acceptor substrate specificities and other biochemical parameters. In vitro enzymatic analysis also showed that one linkage can be synthesized by multiple enzymes and one enzyme may be responsible for synthesis of multiple gangliosides. Following the cloning of the ganglioside synthase genes, the promoters of the key synthase genes in the ganglioside biosynthetic pathway have been cloned and analyzed. All of the promoters are TATA-less, lacking a CCAAT box but containing GC-rich boxes, characteristic of the housekeeping genes, although transcription of ganglioside synthase genes is subject to complex developmental and tissue-specific regulation. A set of cis-acting elements and transcription factors, including Sp1, AP2, and CREB, function in the proximal promoters. Negative-regulatory regions have also been defined in most of the promoters. We present here an overview of these genes and their transcriptional regulation. Keywords glycosyltransferase; ganglioside; ganglioside synthase; gene cloning; transcription regulation; transcription factors Cloning of the Ganglioside Synthase (Glycosyltransferase) GenesGanglioside synthases are glycosyltransferases (GTs) that transfer sugar residues from an activated donor substrate, usually a nucleotide-sugar, to a specific acceptor, which may be a lipid, protein, or growing oligosaccharide. GTs are typically grouped into families based on the type of sugar they transfer (i.e., galactosyltransferases, sialyltransferases, and like). Many GT genes have been identified by molecular cloning or homology search of the available genomic databases and have been classified into families by amino-acid-sequence similarities [1,2] (available at http://afmb.crns-mrs.fr/CAZY and http:// glycob.oupjournals.org). Despite the fact that many GTs recognize identical donor or acceptor substrates, surprisingly limited sequence homology exists among different families [2]. However, common structural features are found among mammalian transferases: they are almost all classified as type II integral membrane proteins, with a short amino-terminal cytoplasmic tail, a membrane-anchoring domain, a short proteolytically sensitive stem region, and a large catalytic domain that includes the carboxyl terminus [3]. In addition, analysis of crystal structures of GTs shows that structural folds appear to be more conserved than sequence similarities since only a few topologies exists for most of the GT families NIH Public Access although there is a large variability in the acceptor-binding domain [4]. The c...

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Studies on the Biosynthesis of Gangliosides

Cited by 50 publications

References 18 publications

Expression Cloning of Mouse cDNA of CMP-NeuAc:Lactosylceramide α2,3-Sialyltransferase, an Enzyme That Initiates the Synthesis of Gangliosides

Expression Cloning of Mouse cDNA of CMP-NeuAc:Lactosylceramide α2,3-Sialyltransferase, an Enzyme That Initiates the Synthesis of Gangliosides

Mice with disrupted GM2/GD2 synthase gene lack complex gangliosides but exhibit only subtle defects in their nervous system.

Cloning and Transcriptional Regulation of Genes Responsible for Synthesis of Gangliosides

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