Intracellular Galectin-9 controls dendritic cell function by maintaining plasma membrane rigidity

Querol Cano, L.; Tagit, O.; van Duffelen, A.; Dieltjes, S.; Buschow, S. I.; Niki, T.; Hirashima, M.; Joosten, B.; van den Dries, K.; Cambi, A.; Figdor, C. G.; van Spriel, A. B.

doi:10.1101/739797

bioRxiv · 10.1101/739797

Intracellular Galectin-9 controls dendritic cell function by maintaining plasma membrane rigidity

Querol Cano, L.·Tagit, O.·van Duffelen, A.·Dieltjes, S.·Buschow, S. I.·Niki, T.·Hirashima, M.·Joosten, B.·van den Dries, K.·Cambi, A.·Figdor, C. G.·van Spriel, A. B.

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Abstract

Extracellular Galectins constitute a novel mechanism of membrane protein organisation at the cell surface. Although Galectins are also highly expressed intracellularly, their cytosolic functions are poorly understood. Here, we investigated the role of Galectin-9 in dendritic cell (DC) surface organisation and function. By combining functional, super-resolution and atomic force microscopy experiments to analyse membrane stiffness, we identified intracellular Galectin-9 to be indispensable for plasma membrane integrity and structure in DCs. Galectin-9 knockdown studies revealed intracellular Galectin-9 to directly control cortical membrane structure via modulating Rac1 activity, providing the underlying mechanism of Galectin-9-dependent actin cytoskeleton organisation. Consequent to its role in maintaining plasma membrane structure, phagocytosis studies revealed that Galectin-9 was essential for C-type lectin receptor-mediated pathogen uptake by human DCs. This was confirmed by the impaired phagocytic capacity of Galectin-9-null murine DCs. Together, this study demonstrates a novel role for intracellular Galectin-9 in modulating DC function, which may be evolutionary conserved.

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Querol Cano, L., Tagit, O., van Duffelen, A., Dieltjes, S., Buschow, S. I., Niki, T., Hirashima, M., Joosten, B., van den Dries, K., Cambi, A., Figdor, C. G., van Spriel, A. B.. 2019-08-20. Intracellular Galectin-9 controls dendritic cell function by maintaining plasma membrane rigidity. https://doi.org/10.1101/739797

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