Evidence that Molecules on the Surface of One Cell Can Adhere to the Oligosaccharide Portion of Gangliosides on the Surface of Another Cell

Schengrund, Cara Lynne

doi:10.1159/000109414

Cited by 12 publications

(4 citation statements)

References 25 publications

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“…Study of ganglioside-protein interactions has traditionally focused on the contribution of the oligosaccharide moiety of gangliosides (Schengrund 1995). However, increasing evidence has highlighted the contribution of long-chain fatty acyl ceramides, not only to glycosphingolipid-protein interactions (Kronke 1999), but also to membrane organization and function of immune cells (Iwabuchi et al 2008;Sonnino et al 2009).…”

Section: Discussionmentioning

confidence: 99%

Ganglioside-binding specificities of E. coli enterotoxin LT-IIc: Importance of long-chain fatty acyl ceramide

et al. 2012

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Bacterial heat-labile (LT) enterotoxins signal through tightly regulated interactions with host cell gangliosides. LT-IIa and LT-IIb of Escherichia coli bind preferentially to gangliosides with a NeuAcα2-3Galβ1-3GalNAc terminus, with key distinctions in specificity. LT-IIc, a newly discovered E. coli LT, is comprised of an A polypeptide with high homology, and a B polypeptide with moderate homology, to LT-IIa and LT-IIb. LT-IIc is less cytotoxic than LT-IIa and LT-IIb. We theorized that LT-IIc-host cell interaction is regulated by specific structural attributes of immune cell ganglioside receptors and designed experiments to test this hypothesis. Overlay immunoblotting to a diverse array of neural and macrophage gangliosides indicated that LT-IIc bound to a restrictive range of gangliosides, each possessing a NeuAcα2-3Galβ1-3GalNAc with a requisite terminal sialic acid. LT-IIc did not bind to GM1a with short-chain fatty acyl ceramides. Affinity overlay immunoblots, constructed to a diverse array of known ganglioside structures of murine peritoneal macrophages, established that LT-IIc bound to GM1a comprised of long-chain fatty acyl ceramides. Findings were confirmed with LT-IIc also binding to GM1a of RAW264.7 cells, comprised of a long-chain fatty acyl ceramide. Thus, LT-IIc-ganglioside binding differs distinctly from that of LT-IIa and LT-IIb. LT-IIc binding is not just dependent on carbohydrate composition, but also upon the orientation of the oligosaccharide portion of GM1a by the ceramide moiety. These studies are the first demonstration of LT-ganglioside dependence upon ceramide composition and underscore the contribution of long-chain fatty acyl ceramides to host cell interactions.

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Section: Discussionmentioning

confidence: 99%

Ganglioside-binding specificities of E. coli enterotoxin LT-IIc: Importance of long-chain fatty acyl ceramide

et al. 2012

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“…Gangliosides also serve as receptors for bacterial organisms such as enterotoxigenic E. coli (22) and Pseudomonas aeruginosa (2). In several biological systems, cell surface gangliosides are postulated to adhere to specific binding molecules on the surfaces of other cells, via their oligosaccharide portions (29).…”

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confidence: 99%

Specific binding of Haemophilus influenzae to minor gangliosides of human respiratory epithelial cells

et al. 1997

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Gangliosides are sialylated glycosphingolipids that serve as receptors for various bacteria. To investigate endogenous gangliosides of human respiratory epithelial cells as potential receptors for Haemophilus influenzae, three strains, including nontypeable H. influenzae (NTHI) 1479, and isogenic fimbriated (f ؉) and nonfimbriated (f 0) H. influenzae type b 770235, were 3 H labeled and overlaid on two-dimensional thin-layer chromatography (TLC) plates containing either purified HEp-2 gangliosides or murine brain gangliosides. NTHI 1479 bound exclusively to two distinct minor ganglioside doublets, with mobilities near that of G M1. These minor gangliosides comprised only 14.2 and 9.4% of the total, respectively. NTHI 1479 also bound to a distinct ganglioside of human macrophages whose chromatographic mobilities closely resemble those of one of the NTHI-binding gangliosides of HEp-2 cells. H. influenzae type b 770235 f ؉ and f 0 each bound to a different minor HEp-2 ganglioside doublet, with proportionately weaker affinity for a major ganglioside doublet. Remarkably, none of the three strains bound to any murine brain gangliosides. Moreover, when 80 to 90% of sialic acid residues were enzymatically removed from HEp-2 gangliosides, NTHI 1479 binding was proportionately impaired, compared with untreated controls. Our findings support a role for specific gangliosides of specific cells as receptors for H. influenzae strains. Our findings further demonstrate that individual minor gangliosides possess unique biological properties.

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“…Gangliosides function as receptors for a variety of bacteria and bacterial products [19,20]. Specific binding molecules on bacterial cell surfaces adhere to host cell gangliosides via their oligosaccharide chains [21]. Earlier studies, including work of our laboratory, implicated gangliosides as receptors for NTHI [5,10].…”

Section: Discussionmentioning

confidence: 99%

NontypeableHaemophilus influenzae-binding gangliosides of human respiratory (HEp-2) cells have a requisite lacto/neolacto core structure

Berenson¹,

Sayles²,

Huang³

et al. 2005

FEMS Immunology &Amp; Medical Microbiology

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Nontypeable Haemophilus influenzae (NTHI) are a major cause of human infections. We previously demonstrated high affinity and high specificity binding of NTHI to minor gangliosides of human respiratory (HEp-2) cells and macrophages, but not to brain gangliosides. We further identified the NTHI-binding ganglioside of human macrophages as alpha2,3-sialylosylparagloboside (IV3NeuAc-nLcOse4Cer, nLM1), which possesses a neolacto core structure that is absent in brain gangliosides. This supported a hypothesis that lacto/neolacto core carbohydrates are critical for NTHI-ganglioside binding. To investigate, we determined the core carbohydrate structure of NTHI-binding gangliosides of HEp-2 cells, through multiple approaches, including specific enzymatic degradation, mass spectral analysis and gas-liquid chromatography. Our analyses denote the following critical structural attributes of NTHI-binding gangliosides: (1) a conserved lacto/neolacto core structure; (2) requisite sialylation, which may be either internal or external, with alpha2,3 (human macrophages) or alpha2,6 (HEp-2 cells) anomeric linkages; (3) internalized galactose residues. Mass spectral and gas chromatographic analyses confirm that NTHI-binding gangliosides of HEp-2 cells possess lacto/neolacto carbohydrate cores and identify the structure of the major peak as NeuAcalpha2-6Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glcbeta1-1Cer (alpha2,6-sialosylparagloboside, nLM1). Collectively, our studies denote NTHI-binding gangliosides as lacto/neolacto series structures.

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Evidence that Molecules on the Surface of One Cell Can Adhere to the Oligosaccharide Portion of Gangliosides on the Surface of Another Cell

Cited by 12 publications

References 25 publications

Ganglioside-binding specificities of E. coli enterotoxin LT-IIc: Importance of long-chain fatty acyl ceramide

Ganglioside-binding specificities of E. coli enterotoxin LT-IIc: Importance of long-chain fatty acyl ceramide

Specific binding of Haemophilus influenzae to minor gangliosides of human respiratory epithelial cells

NontypeableHaemophilus influenzae-binding gangliosides of human respiratory (HEp-2) cells have a requisite lacto/neolacto core structure

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