Biological Sciences; Molecular Biology; Cell BiologyEndogenous extracellular Galectins constitute a novel mechanism of membrane protein organization 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 organization and function. By combining functional, super-resolution and atomic force microscopy experiments to analyze 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 by modulating Rac1 activity, providing the underlying mechanism of Galectin-9-dependent actin cytoskeleton organization. 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 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 evolutionarily conserved.

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Department of Gastroenterology & Hepatology

Querol Cano, L. (Laia), Tagit, O. (Oya), Dolen, Y. (Yusuf), van Duffelen, A. (Anne), Dieltjes, S. (Shannon), Buschow, S. I., … van Spriel, A.B. (Annemiek B.). (2019). Intracellular Galectin-9 Controls Dendritic Cell Function by Maintaining Plasma Membrane Rigidity. iScience, 22, 240–255. doi:10.1016/j.isci.2019.11.019