Biochemistry and Function of Sialidases

Saito, Megumi; Yu, Robert K.

doi:10.1007/978-1-4757-9504-2_8

Cited by 69 publications

(76 citation statements)

References 331 publications

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“…Studies of several pathogenic micro-organisms have implicated sialidase as a major virulence determinant [32]. Sialidase is also produced by some viridans streptococci, including S. oralis [33], which is probably the most pathogenic species of this group, and the production of this enzyme may play a pivotal role in the preponderance of this organism in extra-oral infections.…”

Section: Discussionmentioning

confidence: 99%

Isolation and characterisation of sialidase from a strain of Streptococcus oralis

Byers¹,

Tarelli²,

Homer³

et al. 2000

Journal of Medical Microbiology

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Streptococcus oralis, the most virulent of the viridans streptococci, produces a sialidase and this exo-glycosidase has been implicated in the disease process of a number of pathogens. The sialidase of S. oralis strain AR3 was purified in order to understand the characteristics of this putative virulence determinant. The enzyme isolated as a high mol. wt aggregate (c. 325 kDa) was purified 4520-fold from late exponential phase cultures by a combination of ultrafiltration, ammonium sulphate precipitation, ionexchange and gel filtration chromatography. The sialidase component had a mol. wt of 144 kDa as determined by SDS-PAGE analysis. The purified sialidase released Nacetylneuraminic acid from a range of sialoglycoconjugates including human AE 1 -acid glycoprotein, bovine submaxillary mucin, colominic acid and sialyl-AE2,3-and sialyl-AE2,6-lactose. Also, N-glycolylneuraminic acid was cleaved from bovine submaxillary mucin. The sialidase had a K m of 11.8 ìM for AE 1 -acid glycoprotein, was active over a broad pH range with a pH optimum of 6.0 and cleaved AE2,3-, AE2,6-and AE2-8-sialyl glycosidic linkages with a marked preference for AE2,3-linkages. The enzyme was competitively inhibited by the sialic acid derivative, 2,3-dehydro-N-acetylneuraminic acid, with a K IC of 1.2 ìM. The characteristics of the purified sialidase would support a nutritional role for this enzyme that may be significant in the proliferation of this organism in the oral cavity and at extra-oral sites in association with life-threatening infections.

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Section: Discussionmentioning

confidence: 99%

Isolation and characterisation of sialidase from a strain of Streptococcus oralis

Byers¹,

Tarelli²,

Homer³

et al. 2000

Journal of Medical Microbiology

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“…Cells-Sialidase activity assay performed at pH 3.8 on GD1a ganglioside, without detergent in the reaction mixture, conclusively allows determination of the plasma membrane-associated sialidase activity with very minor or no contamination by lysosomal enzyme(s) activity (41). Under these experimental conditions, MmNEU3 activity on GD1a ranged from 0.1 to 0.3 milliunits/mg cell protein.…”

Section: Mmneu3 Activity and Structure Of Gangliosides In Cos-7mentioning

confidence: 94%

The Plasma Membrane-associated Sialidase MmNEU3 Modifies the Ganglioside Pattern of Adjacent Cells Supporting Its Involvement in Cell-to-Cell Interactions

Papini

Anastasia

Tringali

et al. 2004

Journal of Biological Chemistry

131

142

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We describe herein the enzyme behavior of MmNEU3, the plasma membrane-associated sialidase from mouse (Mus musculus). MmNEU3 is localized at the plasma membrane as demonstrated directly by confocal microscopy analysis. In addition, administration of the radiolabeled ganglioside GD1a to MmNEU3-transfected cells, under conditions that prevent lysosomal activity, led to its hydrolysis into ganglioside GM1, further indicating the plasma membrane topology of MmNEU3. Metabolic labeling with [1-3 H]sphingosine allowed the characterization of the ganglioside patterns of COS-7 cells. MmNEU3 expression in COS-7 cells led to an extensive modification of the cell ganglioside pattern, i.e. GM3 and GD1a content was decreased to about one-third compared with mock-transfected cells. At the same time, a 35% increase in ganglioside GM1 content was observed. Mixed culture of MmNEU3-transfected cells with [1-3 H]sphingosine-labeled cells demonstrates that the enzyme present at the cell surface is able to recognize gangliosides exposed on the membrane of nearby cells. Under these experimental conditions, the extent of ganglioside pattern changes was a function of MmNEU3 transient expression. Overall, the variations in GM3, GD1a, and GM1 content were very similar to those observed in the case of [1-3 H]sphingosine-labeled MmNEU3-transfected cells, indicating that the enzyme mainly exerted its activity toward ganglioside substrates present at the surface of neighboring cells. These results indicate that the plasma membrane-associated sialidase MmNEU3 is able to hydrolyze ganglioside substrates in intact living cells at a neutral pH, mainly through cell-to-cell interactions. Glycosphingolipids (GSLs)1 expressed at the cell surface are well known as modulators of several aspects of signal transduction processes involved in the control of cell proliferation, survival, and differentiation (1). GSLs in the plasma membrane are able to interact laterally with other membrane molecules modulating their properties (cis-interactions). Lipid rafts or membrane microdomains result from dynamic clustering of sphingolipids and cholesterol to form the so-called sphingolipid-enriched domain (SED) or lipid rafts (2). These structures move within the fluid bilayer and function as platforms for the attachment of proteins when membranes are moved around the cell and during signal transduction (3, 4). In addition, the expression pattern of GSLs in several cells and tissues undergoes deep changes during development and neoplastic transformation (5). These events are usually characterized by dramatic changes in cell recognition, suggesting that GSLs as cell surface antigens could play relevant roles as receptor sites in cell-cell recognition (trans-interaction). The receptor role of GSLs has been hypothesized in the case of microbial infections based on their ability to interact with bacterial toxins and microbial lectins (6, 7). Conformational analysis confirms that the orientation of the oligosaccharide chains of glycolipids at the cell surface complies wit...

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“…Sialidases (neuraminidases) are glycohydrolytic enzymes that remove sialic acid residues from glycoconjugates (Saito and Yu, 1995). They show a wide distribution in nature, from viruses to vertebrates.…”

Section: Discussionmentioning

confidence: 99%

“…Sialidases have a wide distribution in nature among viruses, bacteria, protozoa, and vertebrates (Svennerholm, 1963;Saito and Yu, 1995). So far, 4 types of sialidases have been identified in humans and characterized according to their subcellular distribution, substrate specificity, and stability.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the human sialidase Neu4 gene promoter

Seyrantepe¹,

Delman²

2014

Turk J Biol

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There are 4 different sialidases that have been described in humans: lysosomal (Neu1), cytoplasmic (Neu2), plasma membrane (Neu3), and lysosomal/mitochondrial (Neu4). Previously, we have shown that Neu4 has a broad substrate specificity and is active against glyco-conjugates, including G M2 ganglioside, at the acidic pH of 3.2. An overexpression of Neu4 in transfected neuroglia cells from a Tay-Sachs patient shows a clearance of accumulated G M2 , indicating the biological importance of Neu4. In this paper, we aimed to characterize a minimal promoter region of the human Neu4 gene in order to understand the molecular mechanism regulating its expression. We cloned 7 different DNA fragments from the human Neu4 promoter region into luciferase expression vectors for a reporter assay and also performed an electrophoretic mobility shift assay to demonstrate the binding of transcription factors. We demonstrated that -187 bp upstream of the Neu4 gene is a minimal promoter region for controlling transcription from the human Neu4 gene. The electrophoretic mobility shift assay showed that the minimal promoter region recruits a c-myc transcription factor, which might be responsible for regulation of Neu4 gene transcription. The data we obtained might be useful to discover small molecules, which control selective high expression of the human Neu4 gene, resulting in the normal morphological phenotype in the lysosomes of Tay-Sachs patients.

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Biochemistry and Function of Sialidases

Cited by 69 publications

References 331 publications

Isolation and characterisation of sialidase from a strain of Streptococcus oralis

Isolation and characterisation of sialidase from a strain of Streptococcus oralis

The Plasma Membrane-associated Sialidase MmNEU3 Modifies the Ganglioside Pattern of Adjacent Cells Supporting Its Involvement in Cell-to-Cell Interactions

Characterization of the human sialidase Neu4 gene promoter

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