Structure and Localization of Gangliosides

Yu, Robert K.; Saito, Megumi

doi:10.1007/978-1-4757-5955-6_1

Cited by 88 publications

(68 citation statements)

References 169 publications

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“…Anti-ganglioside antibodies have become a popular tool for localizing gangliosides in neuronal and nonneuronal tissues (Schwarz and Futerman 1996;Yu and Saito 1989). However, because of the unique solubility properties of lipids (Stein and Stein 1971), and because gangliosides are expressed mainly at the cell surface (van Echten and Sandhoff 1993), mild fixation, if fixation is needed at all, must be used to localize gangliosides, at least in dissociated cultures, although stronger fixation and permeabilization are presumably needed in whole tissues.…”

Section: Discussionmentioning

confidence: 99%

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Determination of the Localization of Gangliosides Using Anti-ganglioside Antibodies: Comparison of Fixation Methods

Schwarz

Futerman

1997

J Histochem Cytochem.

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SUMMARYMany studies have examined the localization of gangliosides using anti-ganglioside antibodies, although widely differing conclusions have been reached. We now demonstrate that the apparent localization of gangliosides can be greatly influenced by the fixation method. Using monoclonal antibody (MAb) A2B5 (which reacts with a variety of gangliosides), hippocampal neurons were labeled at the cell surface when incubated with the antibody before fixation, but when incubated after fixation the cells displayed a variety of labeling patterns, depending on the fixation method. Biochemical analysis demonstrated that some of the fixatives (particularly acetone and methanol) significantly reduced or completely depleted cellular gangliosides, implying that the immunoreactivity observed with A2B5, and with other antibodies, was not due to gangliosides. When neurons were incubated with an anti-GD1b antibody prefixation, uniform labeling of the plasma membrane was observed, but after ganglioside depletion using biochemical inhibitors of ganglioside synthesis no cell surface labeling was detected. However, even in cells depleted of gangliosides, labeling of both the cell surface and intracellular compartments was observed when the anti-GD1b antibody was applied after fixation. Moreover, after fixation, antibodies to GM4 and GD2 reacted with hippocampal neurons, although these gangliosides are absent from these neurons. In contrast, the JONES antibody (which reacts with 9-O -acetylated GD3) labeled neurons with a similar pattern, essentially irrespective of the fixation method. These observations demonstrate that great care must be taken in assigning gangliosides to specific cell populations or to intracellular locations solely on the basis of use of anti-ganglioside antibodies, and suggest that optimal fixation conditions must be established for each anti-ganglioside antibody. (J Histochem Cytochem 45:611-618, 1997)

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Section: Discussionmentioning

confidence: 99%

“…Most of the proposed functions of gangliosides are related to their localization at the plasma membrane, where they have been shown by biochemical analyses to be enriched (Yu and Saito 1989), although low levels of gangliosides have also been detected in intracellular membranes (Matyas and Morre 1987).…”

mentioning

confidence: 99%

Determination of the Localization of Gangliosides Using Anti-ganglioside Antibodies: Comparison of Fixation Methods

Schwarz

Futerman

1997

J Histochem Cytochem.

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“…Gangliosides are major cell surface determinants and the predominant sialoglycoconjugates of which GM1, GD1a, GD1b, and GT1b are the most abundant gangliosides in the adult mammalian nervous system (Yu and Saito, 1989). These complex gangliosides are structurally related and contain a ceramide lipid anchor, a neutral tetrasaccharide core (Gal ␤3 GalNAc ␤4 Gal ␤4 Glc), and one or more sialic acids.…”

Section: Introductionmentioning

confidence: 99%

Passive Immunization with Anti-Ganglioside Antibodies Directly Inhibits Axon Regeneration in an Animal Model

Lehmann¹,

López²,

Zhang³

et al. 2007

J. Neurosci.

108

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Recent studies have proposed that neurite outgrowth is influenced by specific nerve cell surface gangliosides, which are sialic acidcontaining glycosphingolipids highly enriched in the mammalian nervous system. For example, the endogenous lectin, myelinassociated glycoprotein (MAG), is reported to bind to axonal gangliosides (GD1a and GT1b) to inhibit neurite outgrowth. Clustering of gangliosides in the absence of inhibitors such as MAG is also shown to inhibit neurite outgrowth in culture. In some human autoimmune PNS and CNS disorders, autoantibodies against GD1a or other gangliosides are implicated in pathophysiology. Because of neurobiological and clinical relevance, we asked whether anti-GD1a antibodies inhibit regeneration of injured axons in vivo. Passive transfer of anti-GD1a antibody severely inhibited axon regeneration after PNS injury in mice. In mutant mice with altered ganglioside or complement expression, inhibition by antibodies was mediated directly through GD1a and was independent of complement-induced cytolytic injury. The impaired regenerative responses and ultrastructure of injured peripheral axons mimicked the abortive regeneration typically seen after CNS injury. These data demonstrate that inhibition of axon regeneration is induced directly by engaging cell surface gangliosides in vivo and imply that circulating autoimmune antibodies can inhibit axon regeneration through neuronal gangliosides independent of endogenous regeneration inhibitors such as MAG.

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“…Ganglioside structures are more complex in the nervous system as compared with other organs such as liver, implying specific nervous system biological functions. 21 They are biosynthesized by sequential action of specific glycosyltransferases. The charged sialic acid-containing carbohydrate core projects from the cell surface, while the nonpolar ceramide portion anchors these moieties into the plasma membrane, and anti-ganglioside Abs bind to these carbohydrate moieties.…”

Section: Gangliosidesmentioning

confidence: 99%

Autoantobodies activate small GTPase RhoA to modulate neurite outgrowth

Sheikh

2011

Small GTPases

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Structure and Localization of Gangliosides

Cited by 88 publications

References 169 publications

Determination of the Localization of Gangliosides Using Anti-ganglioside Antibodies: Comparison of Fixation Methods

Determination of the Localization of Gangliosides Using Anti-ganglioside Antibodies: Comparison of Fixation Methods

Passive Immunization with Anti-Ganglioside Antibodies Directly Inhibits Axon Regeneration in an Animal Model

Autoantobodies activate small GTPase RhoA to modulate neurite outgrowth

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