title: Beyond glycoproteins as galectin counterreceptors: tumor-effector T cell growth control via ganglioside GM1 [corrected].
abstract: 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 α(5)β(1) integrin by galectin-1 on carcinoma cells leads to G(1) 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 α(4)/α(5)β(1) integrins elicits Ca(2+)-influx via TRPC5 channels as the relevant response for T effector cell (T(eff)) suppression. Unlike T(eff) 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, T(eff) 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.
authors.affiliation: Department of Neurology and Neurosciences, New Jersey, Medical School-University of Medicine and Dentistry of New Jersey, Newark, USA. ledeenro@umdnj.edu
authors.forename: Robert W
authors.initials: RW
authors.lastname: Ledeen
authors.forename: Gusheng
authors.initials: G
authors.lastname: Wu
authors.forename: Sabine
authors.initials: S
authors.lastname: André
authors.forename: David
authors.initials: D
authors.lastname: Bleich
authors.forename: Guillemette
authors.initials: G
authors.lastname: Huet
authors.forename: Herbert
authors.initials: H
authors.lastname: Kaltner
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kopitz
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Gabius
mesh_terms: D000818:Animals; D023102:Anoikis / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D005677:G(M1) Ganglioside / Q000737:chemistry / Q000276:immunology*; D037161:Galectins / Q000737:chemistry / Q000276:immunology*; D006023:Glycoproteins / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007191:Indazoles; D051379:Mice; D018448:Models, Immunological; D009025:Morpholines; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D011422:Propionates; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D037161:Galectins; D006023:Glycoproteins; D007191:Indazoles; D009025:Morpholines; D011422:Propionates; D005677:G(M1) Ganglioside; C038974:amorolfine; C079489:bindarit