What Cyto- and Histochemistry Can Do to Crack the Sugar Code

Abstract

As letters form the vocabulary of a language, biochemical 'symbols' (the building blocks of oligo-and polymers) make writing molecular messages possible. Compared to nucleotides and amino acids, sugars have chemical properties that facilitate to reach an unsurpassed level of oligomer diversity. These glycans are a part of the ubiquitous cellular glycoconjugates. Cyto-and histochemically, the glycans' structural complexity is mapped by glycophenotyping of cells and tissues using receptors ('readers', thus called lectins), hereby revealing its dynamic spatiotemporal regulation: these data support the concept of a sugar code. When proceeding from work with plant (haem)agglutinins as such tools to the discovery of endogenous (tissue) lectins, it became clear that a broad panel of biological meanings can indeed be derived from the sugar-based vocabulary (the natural glycome incl. post-synthetic modifications) by glycan-lectin recognition in situ. As consequence, the immunocyto-and histochemical analysis of lectin expression is building a solid basis for the steps toward tracking down functional correlations, for example in processes leading to cell adhesion, apoptosis, autophagy or growth regulation as well as targeted delivery of glycoproteins. Introduction of labeled tissue lectins to glycan profiling assists this endeavor by detecting counterreceptor(s) in situ. Combining these tools and their applications strategically will help to take the trip toward the following long-range aim: to compile a dictionary for the glycan vocabulary that translates each message (oligosaccharide) into its bioresponse(s), that is to crack the sugar code.

35 years in plant lectin research: a journey from basic science to applications in agriculture and medicine

“…Proteins ‘reading’ the glycans, the lectins, have revealed the dynamic regulation of glycosylation, both in time and in space. These data support the idea of a ‘sugar code’, the glycome, and lectins being the readers or decoders [ 147 , 148 ]. In contrast to the proteins, the glycans are not encoded in the genome, making it challenging to study their presence and functionality in biological systems.…”

“…Lectins on one hand can read the ‘glyco’code, as is the case in applications where lectins are being used to decipher specific glycostructures (in particular the use of lectins in cytochemistry, histochemistry or as ligands for affinity-based chromatography). On the other hand, it is also clear that lectin-carbohydrate interactions can be the starting point for a signaling cascade, as in many immune responses [ 80 , 116 , 148 ].…”

The marriage of chemokines and galectins as functional heterodimers

“…“The finding that S-type lectins form an evolutionarily related family, with certain residues being critically conserved” [ 137 ] prompted the search for additional homologous proteins by computer-assisted sequence alignment, and then to progressively track all members of this family at the genome level [ 138 ]. In this way, galectins can be viewed in situ as a network of such mediators [ 139 , 140 ].…”

Imitating evolution’s tinkering by protein engineering reveals extension of human galectin-7 activity

“…So far, the study of galectins has mostly focused on separate analysis of each protein. It is now advancing to include the consideration of networking between WT galectins (Habermann et al 2021). Intriguingly, the possibility for hybrids to occur transiently in cells furnishes access to reversible heterobifunctionality built by non-covalently associated CRDs.…”