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Beyond glycoproteins as galectin counterreceptors: tumor‐effector T cell growth control via ganglioside GM1
Author(s) -
Ledeen Robert W.,
Wu Gusheng,
André Sabine,
Bleich David,
Huet Guillemette,
Kaltner Herbert,
Kopitz Jürgen,
Gabius HansJoachim
Publication year - 2012
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2012.06479.x
Subject(s) - microbiology and biotechnology , galectin , anoikis , integrin , galectin 1 , effector , ganglioside , cell growth , t cell , cell adhesion , biology , chemistry , cell , cancer cell , immunology , biochemistry , cancer , genetics , immune system
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.