Intracellular galectin interactions in health and disease

Abstract

In the galectin family, a group of lectins is united by their evolutionarily conserved carbohydrate recognition domains. These polypeptides play a role in various cellular processes and are implicated in disease mechanisms such as cancer, fibrosis, infection, and inflammation. Following synthesis in the cytosol, manifold interactions of galectins have been described both extracellularly and intracellularly. Extracellular galectins frequently engage with glycoproteins or glycolipids in a carbohydrate-dependent manner. Intracellularly, galectins bind to non-glycosylated proteins situated in distinct cellular compartments, each with multiple cellular functions. This diversity complicates attempts to form a comprehensive understanding of the role of galectin molecules within the cell. This review enumerates intracellular galectin interaction partners and outlines their involvement in cellular processes. The intricate connections between galectin functions and pathomechanisms are illustrated through discussions of intracellular galectin assemblies in immune and cancer cells. This underscores the imperative need to fully comprehend the interplay of galectins with the cellular machinery and to devise therapeutic strategies aimed at counteracting the establishment of galectin-based disease mechanisms.

Keywords: Cancer; Galectin; Immune cell; Protein interaction.

Fig. 1

Domain structure of galectin subtypes. Prototype galectins contain one CRD, galectin-1, -2, -5, -7, -10, -11, -13, -14 and − 16. They are often characterized by a dimeric quaternary structure. Tandem repeat-type galectin-4, -6, -8, -9 and 12 are characterized by two CRDs. The only chimera-type galectin with a dynamic proline/tyrosine/glycine-repeat N-terminal domain and one C-terminal CRD is galectin-3. Type-C and Type-N-self-association by the C- or N-terminal domain into oligomeric assemblies have been described

Fig. 2

Intracellular binding partners of galectins in distinct cellular processes. Different cellular localizations and interaction partners of galectins are exemplified on a scheme depicting cellular organelles. Subtypes of prototype and tandem repeat galectins are indicated. E, endosome; LT, lactotransferrin; MVE, multivesicular endosome; SE, sorting endosome; V, transport vesicle