Glycohistochemistry: the why and how of detection and localization of endogenous lectins.
The central dogma of molecular biology limits the downstream flow of genetic information to proteins. Progress from the last two decades of research on cellular glycoconjugates justifies adding the enzymatic production of glycan antennae with information-bearing determinants to this famous and basic pathway. An impressive variety of regulatory processes including cell growth and apoptosis, folding and routing of glycoproteins and cell adhesion/migration have been unravelled and found to be mediated or modulated by specific protein (lectin)-carbohydrate interactions. The conclusion has emerged that it would have meant missing manifold opportunities not to recruit the sugar code to cellular information transfer. Currently, the potential for medical applications in anti-adhesion therapy or drug targeting is one of the major driving forces fuelling progress in glycosciences. In histochemistry, this concept has prompted the introduction of carrier-immobilized carbohydrate ligands (neoglycoconjugates) to visualize the cells' capacity to be engaged in oligosaccharide recognition. After their isolation these tissue lectins will be tested for ligand analysis. Since fine specificities of different lectins can differ despite identical monosaccharide binding, the tissue lectins will eventually replace plant agglutinins to move from glycan profiling and localization to functional considerations. Namely, these two marker types, i.e. neoglycoconjugates and tissue lectins, track down accessible binding sites with relevance for involvement in interactions in situ. The documented interplay of synthetic organic chemistry and biochemistry with cyto- and histochemistry nourishes the optimism that the application of this set of innovative custom-prepared tools will provide important insights into the ways in which glycans can act as hardware in transmitting information during normal tissue development and pathological situations.
Gabius
H J
HJ
Institut für Physiologische Chemie, Tierärztliche Fakultät, Ludwig-Maximilians-Universität München, Veterinärstr. 13, D-80539 München, Germany. gabius@tiph.vetmed.uni-muenchen.de
D017209:Apoptosis; D015415:Biomarkers; D002240:Carbohydrate Sequence; D002455:Cell Division; D006001:Glycoconjugates / Q000737:chemistry*; D006651:Histocytochemistry; D037102:Lectins / Q000145:classification / Q000502:physiology*; D008024:Ligands; D013329:Structure-Activity Relationship
D015415:Biomarkers; D006001:Glycoconjugates; D037102:Lectins; D008024:Ligands