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Galectin-9: From cell biology to complex disease dynamics

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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.

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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.

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  1. Department of Neurobiology and Genetics, Division of Disease Biology, Rajiv Gandhi Centre for Biotechnology, Poojappura, Thiruvananthapuram, 695014, India

    Sebastian John & Rashmi Mishra

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  1. Sebastian John
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Correspondence to Rashmi Mishra.

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Corresponding editor: Veena K Parnaik

[John S and Mishra R 2016 Galectin-9: From cell biology to complex disease dynamics. J. Biosci.]

Supplementary materials pertaining to this article are available on the Journal of Biosciences Website.

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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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John, S., Mishra, R. Galectin-9: From cell biology to complex disease dynamics. J Biosci 41, 507–534 (2016). https://doi.org/10.1007/s12038-016-9616-y

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