Galectins as pattern recognition receptors: structure, function, and evolution

Abstract

Galectins constitute an evolutionary conserved family of ß-galactoside-binding proteins, ubiquitous in mammals and other vertebrate taxa, invertebrates, and fungi. Since their discovery in the 1970s, their biological roles, initially understood as limited to recognition of carbohydrate ligands in embryogenesis and development, have expanded in recent years by the discovery of their immunoregulatory activities. A gradual paradigm shift has taken place in the past few years through the recognition that galectins also bind glycans on the surface of potentially pathogenic microbes, and function as recognition and effector factors in innate immunity. Further, an additional level of functional complexity has emerged with the most recent findings that some parasites "subvert" the recognition roles of the vector/host galectins for successful attachment or invasion.

Fig. 1. Galectin types and structure of the galectin-1/LacNAc complex

a Galectins are classified in three types: “proto” (a), “chimera” (b), and “tandem-repeat” (c); b The structure of the galectin-1/thiodigalactoside (TDG) complex reveals a dimer, which each globular subunit binding a single oligosaccharide

Fig. 2. Subcellular and extracellular localization of galectins

Galectins are synthesized in the cytosol, and can be translocated into the nucleus or secreted to the extracellular space, where they bind to glycans of the extracellular matrix or the cell surface

Fig. 3. Biological roles of galectins upon binding to the cell surface

Galectins can bind to glycans on neighboring cells or to cells and the extracellular matrix, leading to cell adhesion, or to the surface of a single cell resulting in the formation of lattices, and the activation of signaling pathways

Fig. 4. The role of hemocyte galectins on parasite host invasion

a: SEM of oyster hemocytes in the process of engulfing Perkinsus marinus trophozoites (indicated by arrows) in vitro (Gauthier and Vasta; 71). b: Cartoon of the hypothetical process that takes place in the gut and other epithelial surfaces: The oyster galectin CvGal mediates recognition and phagocytosis of P. marinus trophozoites by hemocytes; the trophozoites survive inside the oyster hemocytes, which migrate from the gut via a trans-epithelia route and are transported to other tissues where the parasite proliferates (Tasumi and Vasta 2007)