• anoikis;
  • carcinoma;
  • diabetes;
  • galectin-1;
  • glycosphingolipid;
  • GM1 ganglioside;
  • immune suppression;
  • T cells

Glycoprotein glycan chains, by virtue of structure, topology of presentation and connection to signal-inducing units, are functional galectin counterreceptors. As example, cross-linking of the α5β1 integrin by galectin-1 on carcinoma cells leads to G1 arrest or anoikis. Contact-dependent switching from proliferation to differentiation in cultured neuroblastoma cells (SK-N-MC) also utilizes galectin-1. Activity enhancement of a cell surface sialidase underlies the shift in glycan display to ganglioside GM1. Its pentasaccharide within microdomains becomes the target. Similarly, this recognition pair is upregulated upon T cell activation. Cross-linking of GM1 along with associated α45β1 integrins elicits Ca2+-influx via TRPC5 channels as the relevant response for T effector cell (Teff) suppression. Unlike Teff cells from wild-type mice, those from genetically altered mice lacking GM1 are not suppressed by galectin-1 or regulatory T cells. Similarly, in the context of GM1 deficiency in NOD mice, Teff cells are associated with resistance to regulatory T cell suppression, which is reversed by applied GM1. The broad array of glycosphingolipid structures suggests the possible existence of several novel counterreceptors targeted to endogenous lectins, with sulfatide–galectin-4 interplay within apical delivery serving as recent example.