Intracellular Galectin-9 Controls Dendritic Cell Function by Maintaining Plasma Membrane Rigidity

Laia Querol Cano; Oya Tagit; Yusuf Dolen; Anne van Duffelen; Shannon Dieltjes; Sonja I Buschow; Toshiro Niki; Mitsuomi Hirashima; Ben Joosten; Koen van den Dries; Alessandra Cambi; Carl G Figdor; Annemiek B van Spriel

doi:10.1016/j.isci.2019.11.019

Intracellular Galectin-9 Controls Dendritic Cell Function by Maintaining Plasma Membrane Rigidity

iScience. 2019 Dec 20:22:240-255. doi: 10.1016/j.isci.2019.11.019. Epub 2019 Nov 15.

Affiliations

¹ Department of Tumour Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein 26-28, Nijmegen 6525 GA, The Netherlands.
² Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Wytemaweg 80, Rotterdam 3015 CN, The Netherlands.
³ GalPharma Co., Ltd., Takamatsu, Kagawa 761-0301, Japan; Department of Immunology and Immunopathology, Faculty of Medicine, Kagawa University, Takamatsu, Kagawa, 761-0793, Japan.
⁴ Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein 26-28, 6525 GA Nijmegen, The Netherlands.
⁵ Department of Tumour Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein 26-28, Nijmegen 6525 GA, The Netherlands. Electronic address: annemiek.vanspriel@radboudumc.nl.

Abstract

Endogenous 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.

Keywords: Biological Sciences; Cell Biology; Molecular Biology.