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Journal of Biosciences

, Volume 41, Issue 3, pp 507–534 | Cite as

Galectin-9: From cell biology to complex disease dynamics

  • Sebastian John
  • Rashmi MishraEmail author
Review

ABSTRACT

Galectins is a family of non-classically secreted, β-galactoside-binding proteins that has recently received considerable attention in the spatio-temporal regulation of surface ‘signal lattice’ organization, membrane dynamics, cell-adhesion and disease therapeutics. Galectin-9 is a unique member of this family, with two non-homologous carbohydrate recognition domains joined by a linker peptide sequence of variable lengths, generating isoforms with distinct properties and functions in both physiological and pathological settings, such as during development, immune reaction, neoplastic transformations and metastasis. In this review, we summarize the latest knowledge on the structure, receptors, cellular targets, trafficking pathways and functional properties of galectin-9 and discuss how galectin-9-mediated signalling cascades can be exploited in cancers and immunotherapies.

Keywords

Cancer carbohydrate recognition domain galectin-9 immune-regulation linker peptide 

Notes

Acknowledgements

We thank the Department of Biotechnology, India, for award of Ramalingaswami Fellowship Grant (BT/RLF/Re-entry/16/2011) to RM for this work.

Supplementary material

12038_2016_9616_MOESM1_ESM.pdf (1.7 mb)
ESM 1 (a) Reconstitution of Galectin-9 Glycosphingolipid interaction on the model membranes: Rhodamine B lipid dye labeled Apical Giant Unilamellar Plasma Membrane Vesicles (GPMVs) from MDCK cells, which are enriched in FGL (Forssman glycosphingolipid) show tubulation and vesicle formation upon addition of fluorescently labelled recombinant Gal-9 protein (Dylight Alexa 488), whereas basolateral does not as it lacks Gal-9 clustering partners at a high density. Similarly, Giant Unilamellar Vesicles (GUVs) with FGL show massive tubulation and vesiculation in the presence of Gal-9, suggesting Gal-9 mediated membrane transport mechanisms. (b) Mechanistic model of Gal-9-FGL glycosphingolipid is shown diagrammatically: 1) Secreted Gal-9 binds to apical membrane enriched Forssman glycosphingolipid and 2) leads to apical membrane clustering of FGL by Gal-9 and consequent 3) membrane bending, which generates 4) endocytic vesicles as observed in a) and these vesicles fuse with Trans-Golgi network 5) where the fused endosome deliver Gal-9 that again clusters the FGL enriched Golgi membranes on the luminal side to 6, 7) generate Post-Golgi vesicles that are vectorially delivered to the apical membrane. This circuitry of cargo transport is found to be crucial for cellular polarization and differentiation of epithelial cells (PDF 1.70 MB)

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© Indian Academy of Sciences 2016

Authors and Affiliations

  1. 1.Department of Neurobiology and Genetics, Division of Disease BiologyRajiv Gandhi Centre for BiotechnologyThiruvananthapuramIndia

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