Localization of globoside and forssman glycolipids on erythrocyte membranes

Tillack, Thomas W.; Allietta, Margaretta; Moran, Robert E.; Young, William W.

doi:10.1016/0005-2736(83)90086-x

Cited by 108 publications

(70 citation statements)

References 26 publications

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“…[1][2][3][4][5][6]. The development of this area has occurred over the past two decades, based on key observations such as (i) the distinctive clustering of glycosphingolipids (GSLs) † and͞or glycoproteins, which has been observed by scanning electron microscopy with freeze-fracture (7). GSL clusters were observed even on liposome surfaces prepared without cholesterol (8)…”

mentioning

confidence: 99%

The glycosynapse

Hakomori

2002

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

472

217

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Physically distinguishable microdomains associated with various functional membrane proteins are one of the major current topics in cell biology. Glycosphingolipids present in such microdomains have been used as “markers;” however, the functional role of glycosyl epitopes in microdomains has received little attention. In this review, I have tried to summarize the evidence that glycosyl epitopes in microdomains mediate cell adhesion and signal transduction events that affect cellular phenotypes. Molecular assemblies that perform such functions are hereby termed “glycosynapse” in analogy to “immunological synapse,” the membrane assembly of immunocyte adhesion and signaling. Three types of glycosynapses are so far distinguishable: (i) Glycosphingolipids organized with cytoplasmic signal transducers and proteolipid tetraspanin with or without growth factor receptors; (ii) transmembrane mucin-type glycoproteins with clustered O-linked glycoepitopes for cell adhesion and associated signal transducers at lipid domain; and (iii) N-glycosylated transmembrane adhesion receptors complexed with tetraspanin and gangliosides, as typically seen with the integrin–tetraspanin–ganglioside complex. The possibility is discussed that glycosynapses give rise to a high degree of diversity and complexity of phenotypes

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mentioning

confidence: 99%

The glycosynapse

Hakomori

2002

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

472

217

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“…Cells were fixed with 3% paraformaldehyde in PBS for 20 min at room temperature, quenched with 50 mM NH 4 Cl, and then blocked with 0.2% gelatin in PBS. Cells were incubated overnight with mAb GL-2 at 4°C, then with FITCconjugated anti-human IgM (EY Laboratories) and Alexa 594-conjugated cholera toxin (Molecular Probes) or monoclonal anti-SM, Vj41 (17).…”

Section: Methodsmentioning

confidence: 99%

Carbohydrate-dependent signaling from the phosphatidylglucoside-based microdomain induces granulocytic differentiation of HL60 cells

Nagatsuka

Miki

Kasama

et al. 2003

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

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“…They contain membrane microdomains, often referred to as lipid rafts and/or caveolae, enriched in glycosphingolipids (GSLs), 1 specific proteins, and cholesterol (1-3). Being operationally defined, i.e.…”

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confidence: 99%

Accumulation of Glycosphingolipids in Niemann-Pick C Disease Disrupts Endosomal Transport

Vruchte

Lloyd-Evans

Veldman

et al. 2004

Journal of Biological Chemistry

168

138

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Glycosphingolipids are endocytosed and targeted to the Golgi apparatus but are mistargeted to lysosomes in sphingolipid storage disorders. Substrate reduction therapy utilizes imino sugars to inhibit glucosylceramide synthase and potentially abrogate the effects of storage. Niemann-Pick type C (NPC) disease is a disorder of intracellular transport where glycosphingolipids (GSLs) and cholesterol accumulate in endosomal compartments. The mechanisms of altered intracellular trafficking are not known but may involve the mistargeting and disrupted function of proteins associated with GSL membrane microdomains. Membrane microdomains were isolated by Triton X-100 and sucrose density gradient ultracentrifugation. High pressure liquid chromatography and mass spectrometric analysis of NPC1 ؊/؊ mouse brain revealed large increases in GSL. Sphingosine was also found to be a component of membrane microdomains, and in NPC liver and spleen, large increases in cholesterol and sphingosine were found. GSL and cholesterol levels were increased in mutant NPC1-null Chinese hamster ovary cells as well as U18666A and progesterone induced NPC cell culture models. However, inhibition of GSL synthesis in NPC cells with N-butyldeoxygalactonojirimycin led to marked decreases in GSL but only small decreases in cholesterol levels. Both annexin 2 and 6, membrane-associated proteins that are important in endocytic trafficking, show distorted distributions in NPC cells. Altered BODIPY lactosylceramide targeting, decreased endocytic uptake of a fluid phase marker, and mistargeting of annexin 2 (phenotypes associated with NPC) are reversed by inhibition of GSL synthesis. It is suggested that accumulating GSL is part of a mislocalized membrane microdomain and is responsible for the deficit in endocytic trafficking found in NPC disease.Increasing evidence suggests that the membranes of eukaryotic cells are not homogeneously fluid. They contain membrane microdomains, often referred to as lipid rafts and/or caveolae, enriched in glycosphingolipids (GSLs), 1 specific proteins, and cholesterol (1-3). Being operationally defined, i.e. by detergent insolubility and low buoyant density, the natural (in situ) existence of such membrane microdomains has been and continues to be controversial (4). However, they have recently been visualized by using electron microscopy as small structures covering as much as 35% of the cell surface (5). Although membrane microdomains on the cell surface tend to be transient (6), relatively stable microdomains have been visualized in the endocytic pathway (7) where they are proposed to play a role in protein and lipid sorting (8). Many GSL storage diseases, including Niemann-Pick type C (NPC), are often characterized by enlarged liver and spleen as well as severe neurodegeneration. In these diseases, cholesterol and GSLs accumulate in the endocytic pathway because of reduced breakdown. Hence, they may be a useful tool for determining the relative importance of GSLs in endocytic transport. Fibroblasts from patients suffering f...

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Localization of globoside and forssman glycolipids on erythrocyte membranes

Cited by 108 publications

References 26 publications

The glycosynapse

The glycosynapse

Carbohydrate-dependent signaling from the phosphatidylglucoside-based microdomain induces granulocytic differentiation of HL60 cells

Accumulation of Glycosphingolipids in Niemann-Pick C Disease Disrupts Endosomal Transport

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