Ah, sweet mystery of death! Galectins and control of cell fate

Abstract

Control of cell death is critical in eukaryotic development, immune system homeostasis, and control of tumorigenesis. The galectin family of lectins is implicated in all of these processes. Other families of molecules function as death receptors or death effectors, but galectins are uniquely capable of acting both extracellularly and intracellularly to control cell death. Extracellularly, galectins cross-link glycan ligands to transduce signals that lead directly to death or that influence other signals regulating cell fate. Intracellular expression of galectins can modulate other signals controlling cell viability. Individual galectins can act on multiple cell types, and multiple galectins can act on the same cell. Understanding how galectins regulate cell viability and function will broaden our knowledge of the roles of galectins in basic biological processes and facilitate development of therapeutic applications for galectins in autoimmunity, transplant-related disease, and cancer.

Galectin-3 Induces Death of Candida Species Expressing Specific β-1,2-Linked Mannans

“…In time course experiments, we observed negligible death after galectin-3 binding at 30 min, with dead cells becoming apparent at 60 -90 min and maximal death observed after 120 min binding of galectin-3 (data not shown). At longer time points (4 and 6 h) the effects of galectin-3 were confounded by proliferation of the surviving cells (data not shown), so we limited the assays to 2 h. Intriguingly, in studies of galectin-3-and galectin-1-induced death of mammalian lymphocytes and lymphoid cell lines, 100% cell death is also not observed, although all cells in the populations examined bind the galectins (13,58,59). As glycosylation is not templated, and factors such as residence time in the Golgi apparatus will affect the type and abundance of glycans added to a glycoprotein (60), subtle differences in glycosylation or density of critical ligands on the surface of cells may regulate the susceptibility of the cells to galectin-3.…”

“…The 14 mammalian galectins are divided into three subgroups, monomeric, tandem repeat, and chimeric, based on domain structure. Galectin-3 is the only member of the chimera-type galectin subgroup, with a CRD in the C terminus and a distinct N-terminal domain that mediates oligomerization of the lectin into pentamers upon binding multivalent saccharide ligands (13,42,43). As mentioned above, galectin-3 is highly expressed in macrophages and immature dendritic cells; expression is up-regulated in activated macrophages and is down-regulated during dendritic cell maturation (37,44).…”

“…Recently, it has become apparent that the galectin family of lectins can also participate in the innate immune defense against pathogens (12). Galectins are present in all multicellular organisms, including worms, sponges, multicellular fungi, and insects (13)(14)(15)(16)(17)(18)(19). Galectins are PRRs in several types of organisms, and many mammalian pathogens express saccharide structures that are recognized by galectins.…”

A Sexual Dimorphism in Intrathymic Sialylation Survey Is Revealed by thetrans-Sialidase fromTrypanosoma cruzi

“…In this study, we postulate a sialylation-dependent checkpoint in the thymic compartment working on the DP thymocyte population in males. Despite its known participation in thymocyte and T cell apoptosis (2,45), the presence of terminal ␣ (2, 3) sialyl residues (the only substrate for the TS) does not interfere with the galectin-1 binding and therefore it seems not to be involved. However, the possibility to alter the accessibility of the CD43 glycoconjugates to the galectin-1 by sialylation/desialylation of its terminal galactoses remains.…”

“…During the maturation process, the surface glycoconjugates found in the different subsets of thymocytes display distinctive sialylation patterns whose physiologic significance still remains largely unknown. These glycoconjugate decoration patterns constitute an issue of growing research interest and are due to the developmentally regulated expression of sialyl transferases along the T cell maturation process (1,2). It is hypothesized that the acquisition of the sialyl residue signals the trafficking of the thymocytes, given its ability to mask terminal sugars that works as potential binders to endogenous lectins and, in fact, the sialylation of the CD8 was shown critical in its binding affinity to the MHC (3-7).…”