How adhesion/growth-regulatory galectins-1 and -3 attain cell specificity: case study defining their target on neuroblastoma cells (SK-N-MC) and marked affinity regulation by affecting microdomain organization of the membrane

Galectins are potent effectors with conspicuous cell-type-specific activity profile. Its occurrence poses the question on the nature of the underlying biochemical determinants, in human SK-N-MC neuroblastoma cells involved in negative growth regulation. Since increase of surface presentation of gang...

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Hauptverfasser: Kopitz, Jürgen (VerfasserIn) , Bergmann, Marion (VerfasserIn) , Gabius, Hans-Joachim (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 28 July 2010
In: IUBMB life
Year: 2010, Jahrgang: 62, Heft: 8, Pages: 624-628
ISSN:1521-6551
DOI:10.1002/iub.358
Online-Zugang:Resolving-System, kostenfrei, Volltext: https://doi.org/10.1002/iub.358
Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/iub.358
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Verfasserangaben:Jürgen Kopitz, Marion Bergmann and Hans-Joachim Gabius

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520 |a Galectins are potent effectors with conspicuous cell-type-specific activity profile. Its occurrence poses the question on the nature of the underlying biochemical determinants, in human SK-N-MC neuroblastoma cells involved in negative growth regulation. Since increase of surface presentation of ganglioside GM1 and homodimeric galectin-1 precedes growth inhibition, a direct interaction is suggested. We thus examined cell binding depending on glucosylceramide synthesis. It was drastically reduced by N-butyldeoxynojirimycin and threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, adding decisive evidence for the assumed galectin/ganglioside binding. Glycoproteins do not compensate ganglioside depletion which was verified by measuring lipid-bound sialic acid. Binding affinity is significantly lowered by disrupting microdomain integrity, also effective for the competitive inhibitor galectin-3. This was caused by cell treatment with either 2-hydroxypropyl-β-cyclodextrin or filipin III. In this cell system, target specificity and topology of ligand presentation act together to enable high-affinity binding. © 2010 IUBMB IUBMB Life, 62(8): 624-628, 2010. 
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