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
✍ Scribed by Jürgen Kopitz; Marion Bergmann; Hans-Joachim Gabius
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 244 KB
- Volume
- 62
- Category
- Article
- ISSN
- 1521-6543
- DOI
- 10.1002/iub.358
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✦ Synopsis
Abstract
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.