How galectins have become multifunctional proteins

Gabriel García Caballero¹, Herbert Kaltner¹, Tanja J. Kutzner¹, Anna-Kristin Ludwig¹, Joachim C. Manning¹, Sebastian Schmidt¹, Fred Sinowatz² and Hans-Joachim Gabius¹

Institute of ¹Physiological Chemistry and ²Anatomy, Histology and Embryology, Faculty of Veterinary Medicine, Ludwig-Maximilians-University Munich, Munich, Germany

Offprint requests to: Hans-Joachim Gabius, PhD, Institut für Physiologische Chemie, Tierärztliche Fakultät, Ludwig-Maximilians-Universität München, Veterinärstr. 13, 80539 München, Germany. e-mail: gabius@tiph.vetmed.uni-muenchen.de, gabius@lectins.de

Summary. Having identified glycans of cellular glycoconjugates as versatile molecular messages, their recognition by sugar receptors (lectins) is a fundamental mechanism within the flow of biological information. This type of molecular interplay is increasingly revealed to be involved in a wide range of (patho)physiological processes. To do so, it is a vital prerequisite that a lectin (and its expression) can develop more than a single skill, that is the general ability to bind glycans. By studying the example of vertebrate galectins as a model, a total of five relevant characteristics is disclosed: i) access to intra- and extracellular sites, ii) fine-tuned gene regulation (with evidence for co-regulation of counterreceptors) including the existence of variants due to alternative splicing or single nucleotide polymorphisms, iii) specificity to distinct glycans from the glycome with different molecular meaning, iv) binding capacity also to peptide motifs at different sites on the protein and v) diversity of modular architecture. They combine to endow these lectins with the capacity to serve as multi-purpose tools. Underscoring the arising broad-scale significance of tissue lectins, their numbers in terms of known families and group members have steadily grown by respective research that therefore unveiled a well-stocked toolbox. The generation of a network of (ga)lectins by evolutionary diversification affords the opportunity for additive/synergistic or antagonistic interplay in situ, an emerging aspect of (ga)lectin functionality. It warrants close scrutiny. The realization of the enormous potential of combinatorial permutations using the five listed features gives further efforts to understand the rules of functional glycomics/lectinomics a clear direction. Histol Histopathol 35, 509-539 (2020)

Key words: Adhesion, Glycosylation, Lectin, Proliferation, Sialylation

DOI: 10.14670/HH-18-199