Cloning, Expression, and Chromosomal Mapping of a Human Ganglioside Sialidase

Wada, Tadashi; Yoshikawa, Yuko; Tokuyama, Satoru; Kuwabara, Masaaki; Akita, Hirotoshi; Miyagi, Taeko

doi:10.1006/bbrc.1999.0973

Cited by 132 publications

(118 citation statements)

References 30 publications

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“…Expression of the sialidases consistently fluctuates with cell differentiation, cell growth and malignant transformation . Among the sialidases, Neu3 is a key enzyme for ganglioside degradation, and is unique in localizing mainly in plasma membrane and in hydrolyzing specifically gangliosides Wada et al, 1999;Monti et al, 2000). Gangliosides have been shown to influence various biological processes at cell surfaces and in fact, our recent reports have presented evidence that Neu3 participates in neuronal differentiation (Hasegawa et al, 2000;Da Silva et al, 2005), transmembrane signaling (Sasaki et al, 2003;Kato et al, 2005;Ueno et al, 2006) and carcinogenesis (Kakugawa et al, 2002;Ueno et al, 2006) through ganglioside modulation.…”

Section: Introductionmentioning

confidence: 94%

A crucial role of plasma membrane-associated sialidase in the survival of human cancer cells

et al. 2007

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Section: Introductionmentioning

confidence: 94%

A crucial role of plasma membrane-associated sialidase in the survival of human cancer cells

et al. 2007

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“…For all clinical subtypes of sialidosis, storage products mostly consist of sialylated oligosaccharides and glycoproteins [Thomas, 2001]. For some patients, a several-fold increase of G M3 -and G D3 -gangliosides was reported in systemic organs [UlrichBott et al, 1987] and in the brain [Yoshino et al, 1990], suggesting that sialidase is also involved in degradation of these molecules; however, more recent work has described a separate enzyme, ganglioside sialidase, encoded by the NEU3 gene [Wada et al, 1999;Monti et al, 2000]. Since both NEU3 and NEU1 sialidases were able in vitro to desialilate G M2 -and G M3 -gangliosides into the corresponding asialo-derivatives, the question of which enzyme is implicated in the intralysosomal catabolism of gangliosides remains open [Igdoura et al, 1999;Li et al, 2001].…”

Section: Introductionmentioning

confidence: 99%

Molecular pathology of NEU1 gene in sialidosis

Poupětová²,

et al. 2003

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Communicated by Mark H. PaalmanLysosomal sialidase (EC 3.2.1.18) has a dual physiological function; it participates in intralysosomal catabolism of sialylated glycoconjugates and is involved in cellular immune response. Mutations in the sialidase gene NEU1, located on chromosome 6p21.3, result in autosomal recessive disorder, sialidosis, which is characterized by the progressive lysosomal storage of sialylated glycopeptides and oligosaccharides. Sialidosis type I is a milder, late-onset, normosomatic form of the disorder. Type I patients develop visual defects, myoclonus syndrome, cherry-red macular spots, ataxia, hyperreflexia, and seizures. The severe early-onset form, sialidosis type II, is also associated with dysostosis multiplex, Hurler-like phenotype, mental retardation, and hepatosplenomegaly. We summarize information on the 34 unique mutations determined so far in the sialidase gene, including four novel missense and one novel nonsense mutations found in two Czech and two French sialidosis patients. The analysis of sialidase mutations in sialidosis revealed considerable molecular heterogeneity, reflecting the diversity of clinical phenotypes that make molecular diagnosis difficult. The majority of sialidosis patients have had missense mutations, many of which have been expressed; their effects on activity, stability, intracellular localization, and supramolecular organization of sialidase were studied. A structural model of sialidase allowed us to localize mutations in the sialidase molecule and to predict their impact on the tertiary structure and biochemical properties of the enzyme. Hum Mutat 22:343-352,

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“…Among the sialidases, plasma membrane sialidase (Neu3) is a key enzyme for ganglioside hydrolysis because of its strict substrate preference to gangliosides. To obtain functional evidence regarding Neu3, we previously cloned and characterized the sialidase cDNAs of mammalian origin (4 -7), and we have employed a human Neu3 cDNA (5) in the present study.…”

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confidence: 99%

A Close Association of the Ganglioside-specific Sialidase Neu3 with Caveolin in Membrane Microdomains

Wang¹,

Yamaguchi²,

Wada³

et al. 2002

Journal of Biological Chemistry

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The ganglioside-specific sialidase Neu3 has been suggested to play essential roles in regulation of cell surface functions because of its major localization in the plasma membrane and strict substrate preference for gangliosides involved in signal transduction. Here we show that human Neu3 sialidase is enriched in caveolae microdomains and closely associates with caveolin like other caveolin-binding signaling molecules. Using HeLa cells and Neu3-transfected COS-1 cells, endogenous and exogenous Neu3 was found to co-concentrate caveolin-1 in low density Triton X-100-insoluble membrane fractions on sucrose density gradients of the respective cell extracts, as assessed by enzyme activity assays and immunoblotting with a monoclonal antibody to human Neu3. The presence of a putative caveolin-binding motif within Neu3 prompted us to determine whether Neu3 binds to caveolin-1. In transfectants expressing a polyhistidine-tagged form of Neu3, caveolin-1 co-eluted with Neu3 on affinity column chromatography. A mutation with a single amino acid change in the caveolin-binding motif led to inhibition of recruitment of the sialidase to the microdomain, accompanied by reduction of the enzyme activity. Neu3 also failed to associate with caveolin-enriched microdomains by cholesterol depletion with ␤-cyclodextrin (with concomitant decrease of the sialidase activity), whereas Neu3 was activated by increased caveolin-1 expression. The tight association of Neu3 with caveolin-1 was supported further by co-immunoprecipitation of Neu3 by anti-caveolin-1 antibody. These results strongly suggest that Neu3 functions as a caveolin-related signaling molecule within caveolinrich microdomains.

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Cloning, Expression, and Chromosomal Mapping of a Human Ganglioside Sialidase

Cited by 132 publications

References 30 publications

A crucial role of plasma membrane-associated sialidase in the survival of human cancer cells

A crucial role of plasma membrane-associated sialidase in the survival of human cancer cells

Molecular pathology of NEU1 gene in sialidosis

A Close Association of the Ganglioside-specific Sialidase Neu3 with Caveolin in Membrane Microdomains

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