Differential functional relevance of a plasma membrane ganglioside sialidase in cholinergic and adrenergic neuroblastoma cell lines

Reitzenstein, Carolina; Kopitz, Jürgen; Schuhmann, Vera; Cantz, Michael

doi:10.1046/j.1432-1327.2001.01883.x

Cited by 7 publications

(7 citation statements)

References 19 publications

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“…In neuroblastoma cell lines, Neu3 expression increased during pharmacologically induced neuronal differentiation [140], and Neu3 gene transfection induced neurite outgrowth [140] and enhanced the effect of differentiating agents on the extension or branching of neurites [76]. Conversely, inhibition of plasma membrane sialidase activity resulted in the loss of neuronal differentiation markers [69,70,141]. In cultured hippocampal neurons, Neu3 activity regulated the local GM1 concentration, determining the neurite's axonal fate by a local increase in TrkA activity [142] and affecting axonal regeneration after axotomy [143].…”

Section: Neuron-glia Interactions (Myelination)mentioning

confidence: 99%

Deregulated Sphingolipid Metabolism and Membrane Organization in Neurodegenerative Disorders

et al. 2010

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Sphingolipids are polar membrane lipids present as minor components in eukaryotic cell membranes. Sphingolipids are highly enriched in nervous cells, where they exert important biological functions. They deeply affect the structural and geometrical properties and the lateral order of cellular membranes, modulate the function of several membrane-associated proteins, and give rise to important intra- and extracellular lipid mediators. Sphingolipid metabolism is regulated along the differentiation and development of the nervous system, and the expression of a peculiar spatially and temporarily regulated sphingolipid pattern is essential for the maintenance of the functional integrity of the nervous system: sphingolipids in the nervous system participate to several signaling pathways controlling neuronal survival, migration, and differentiation, responsiveness to trophic factors, synaptic stability and synaptic transmission, and neuron-glia interactions, including the formation and stability of central and peripheral myelin. In several neurodegenerative diseases, sphingolipid metabolism is deeply deregulated, leading to the expression of abnormal sphingolipid patterns and altered membrane organization that participate to several events related to the pathogenesis of these diseases. The most impressive consequence of this deregulation is represented by anomalous sphingolipid-protein interactions that are at least, in part, responsible for the misfolding events that cause the fibrillogenic and amyloidogenic processing of disease-specific protein isoforms, such as amyloid beta peptide in Alzheimer's disease, huntingtin in Huntington's disease, alpha-synuclein in Parkinson's disease, and prions in transmissible encephalopathies. Targeting sphingolipid metabolism represents today an underexploited but realistic opportunity to design novel therapeutic strategies for the intervention in these diseases.

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Section: Neuron-glia Interactions (Myelination)mentioning

confidence: 99%

Deregulated Sphingolipid Metabolism and Membrane Organization in Neurodegenerative Disorders

et al. 2010

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“…Somewhat puzzlingly, both Neu3 silencing (98) and NEU3 overexpression (99) have been shown to stimulate neurite outgrowth. This apparent discrepancy may reflect the differences present in the cholinergic and adrenergic neuroblastoma cell lines in which these experiments were performed (100). NEU3 activity is enriched in membrane microdomains of neuroblastoma cells and co-segregates with GM1 and other lipid raft markers such as flotillin, src family kinases, and glycosylphosphatidylinositol (GPI)-anchored proteins (101).…”

Section: Sialidase Activity Stimulates Axonal Outgrowthmentioning

confidence: 99%

Regulation of Intracellular Signaling by Extracellular Glycan Remodeling

Parker

Kohler

2009

ACS Chem. Biol.

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The plasma membrane of eukaryotic cells is coated with carbohydrates. By virtue of their extracellular position and recognizable chemical features, cell surface glycans mediate many receptor-ligand interactions. Recently, mammalian extracellular hydrolytic enzymes have been shown to modify the structure of cell surface glycans and consequently, alter their binding properties. These cell surface glycan remodeling events can cause rapid changes in critical signal transduction phenomena. This review highlights recent studies on the roles of eukaryotic extracellular sialidases, sulfatases, and a deacetylase in regulation of intracellular signaling. We also describe possible therapies that target extracellular glycan remodeling processes and discuss the potential for new discoveries in this area.The glycocalyx stands between extracellular signals and intracellular responses. But the glycoproteins, glycolipids and proteoglycans that comprise the glycocalyx are not simply a barrier; rather, they serve essential roles in the transduction of signals from the outside to the inside of cells. Indeed, most cell surface receptors are glycosylated and many specifically recognize glycans that are attached to their ligands. Cell surface and extracellular glycans have been demonstrated to play critical roles in the control and modulation of a variety of signal transduction pathways (1-4). For example, in embryonic development, signaling through the Notch receptor requires that the receptor be modified with O-fucose glycans (5). If these glycans are absent, gestational death occurs. In the adult nervous system, the myelin-associated glycoprotein (MAG) binds to glycoproteins and glycolipids on axons, forming signaling complexes that inhibit axonal outgrowth (6). And in the immune system, specific cell surface glycans are essential components of the signal transduction pathways that lead to processes such as B-cell receptor activation and T-cell apoptosis (7,8). Glycosylation also regulates intracellular signal transduction events: for example, the addition of O-linked Nacetylglucosamine (O-GlcNAc) to histone lysine methyl transferase MLL5 activates this enzyme, causing it to methylate histone H3 and thereby leading to cell lineage determination (9).As more signaling roles for glycans are identified, an essential task is to understand the mechanisms that regulate the glycosylation state of a cell or molecule (Figure 1). Most glycans are assembled in the endoplasmic reticulum (ER) and Golgi through the coordinate action of many membrane-associated glycosyltransferases and other glycan-modifying enzymes, such as sulfotransferases and epimerases. ER-and Golgi-resident glycosyltransferases require nucleotide-sugar donors, such as uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc), guanidine diphosphate-fucose (GDP-fucose), and cytidine monophosphate-sialic acids (CMPsialic acids), that are synthesized in the cytoplasm or nucleus. Once assembled in the secretory *To whom correspondence should be addressed (Jennifer.Kohler@UTSou...

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“…Evidence of a possible involvement of this enzyme in the regulation of the sialic acid levels of the cell surface has been produced. For example, in neuroblastoma cells the enzyme triggers selective ganglioside desialylation, and such surface glycolipid modulations are involved in cell growth control and differentiation (23)(24)(25). The plasma membrane sialidase NEU3 3 is characterized by high substrate specificity for ganglioside substrates in the acidic range of pH (26).…”

Section: Glycosphingolipids (Gsls)mentioning

confidence: 99%

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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Differential functional relevance of a plasma membrane ganglioside sialidase in cholinergic and adrenergic neuroblastoma cell lines

Cited by 7 publications

References 19 publications

Deregulated Sphingolipid Metabolism and Membrane Organization in Neurodegenerative Disorders

Deregulated Sphingolipid Metabolism and Membrane Organization in Neurodegenerative Disorders

Regulation of Intracellular Signaling by Extracellular Glycan Remodeling

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

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