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Intracellular galectins control cellular responses commensurate with cell surface carbohydrate composition

Intracellular galectins control cellular responses commensurate with cell surface carbohydrate composition

Glycobiology, January 2020, Volume 30, Issue 1, Pages 36–48
doi: 10.1093/glycob/cwz075

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Abstract

Galectins are β-galactoside-binding animal lectins primarily found in the cytosol, while their carbohydrate ligands are mainly distributed in the extracellular space. Cytosolic galectins are anticipated to accumulate on damaged endocytic vesicles through binding to glycans initially displayed on the cell surface and subsequently located in the lumen of the vesicles, and this can be followed by cellular responses. To facilitate elucidation of the mechanism underlying this process, we adopted a model system involving induction of endocytic vesicle damage with light that targets the endocytosed amphiphilic photosensitizer disulfonated aluminum phthalocyanine (AlPcS2a). We demonstrate the levels of galectins around damaged endosomes are dependent on the composition of carbohydrates recognized by the proteins. By super resolution imaging, galectin-3 and galectin-8 aggregates were found to be distributed in distinct microcompartments. Importantly, galectin accumulation is significantly affected when cell surface glycans are altered. Furthermore, accumulated galectins can direct autophagy adaptor proteins toward damaged endocytic vesicles, which are also significantly affected following alteration of cell surface glycans. We conclude cytosolic galectins control cellular responses reflecting dynamic modifications of cell surface glycans.