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

Authors

  • Jürgen Kopitz,

    Corresponding author
    1. Pathologisches Institut, Abteilung für Angewandte Tumorbiologie, Ruprecht-Karls-Universität, Im Neuenheimer Feld 220, D-69120 Heidelberg, Germany
    • Pathologisches Institut, Abteilung für Angewandte Tumorbiologie, Ruprecht-Karls-Universität, Im Neuenheimer Feld 220, D-69120 Heidelberg, Germany
    Search for more papers by this author
    • Fax: +49 (0)6221 565981

  • Marion Bergmann,

    1. Pathologisches Institut, Abteilung für Angewandte Tumorbiologie, Ruprecht-Karls-Universität, Im Neuenheimer Feld 220, D-69120 Heidelberg, Germany
    Search for more papers by this author
  • Hans-Joachim Gabius

    1. Institut für Physiologische Chemie, Tierärztliche Fakultät, Ludwig-Maximilians-Universität, Veterinärstr. 13, D-80539 München, Germany
    Search for more papers by this author

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.

Ancillary