Network analysis of adhesion/growth‐regulatory galectins and their binding sites in adult chicken retina and choroid

Abstract

The highly ordered multilayered organization of the adult chicken retina is a suitable test model for examining zonal distribution of the members of a bioeffector family. Based on the concept of the sugar code, the functional pairing of glycan epitopes with cognate receptors (lectins) is emerging as a means to explain the control of diverse physiological activities. Having recently completed the biochemical characterization of all seven adhesion/growth-regulatory galectins present in chicken, it was possible to establish how the individual characteristics of their expression profiles add up to shape the galectin network, which until now has not been defined at this level of complexity. This information will also have relevance in explaining the region-specific presence of glycan determinants in the retina, as illustrated in the first part of this study using a panel of nine plant/fungal agglutinins. The following systematic monitoring of the galectins yielded patterns for which quantitative and qualitative differences were detected. Obviously, positivity in distinct layers is not confined to a single protein of this family, e.g. CG-1A, CG-3 or CG-8. These results underline the requirement for network analysis for these proteins that can functionally interact in additive or antagonistic modes. Labeling of the tissue galectins facilitated profiling of their accessible binding sites. It also revealed differences among the galectin family members, highlighting the ability of this method to define binding properties on the level of tissue sections. Methodologically, the detection of endogenous lectins intimates that cognate glycans can become inaccessible, a notable caveat for lectin histochemical studies.

Chicken GRIFIN: Structural characterization in crystals and in solution

“…Implementing the Asn48Lys change, a hallmark of mammalian GRIFINs, made binding of this mutant protein to tissue sections rather insensitive to lactose presence, intimating this position to be a key site for interactions. This result and the presented structural informations build a solid foundation to proceed in the quest to understand GRIFIN's role as lens protein not present, for example, in the retina [17,19,77]. Moreover, they are a step toward completing the structural analysis of the galectin network in a model organism, i.e.…”

Galectins‐1 and ‐3 in Human Intervertebral Disc Degeneration: Non‐Uniform Distribution Profiles and Activation of Disease Markers Involving NF‐κB by Galectin‐1

“…29 Considering initial evidence for functional networking among galectins, it becomes reasonable that upcoming studies proceed with the immunohistochemical analysis of further members of this lectin family (such as Gal-8), at best reaching the level of comprehensive fingerprinting. [45][46][47][48] When setting the distribution profiles of Gal-1 and -3 in relation to tissue degradation, the total scores of immunopositivity significantly correlated with histopathological degeneration and MRI grading. At the level of IVD components, immunopositivity for Gal-1 and -3 at all sites, except for EP and the NP matrix in the case of Gal-1, independently correlated with total histopathological degeneration scores of the specimens.…”

“…In rat NP cells, Gal‐3 knock‐down led to increased susceptibility to FasL‐induced cell death, and a functional cooperation between tumor necrosis factor‐α and Gal‐3 on IL‐1β, IL‐6, and CCL2 expression had been reported . Considering initial evidence for functional networking among galectins, it becomes reasonable that upcoming studies proceed with the immunohistochemical analysis of further members of this lectin family (such as Gal‐8), at best reaching the level of comprehensive fingerprinting …”

Members of the Galectin Network with Deviations from the Canonical Sequence Signature. 2. <i>G</i>alectin-<i>R</i>elated <i>P</i>rotein (GRP)

“…Thus, C-GRP may likely be less prone to self-aggregation in the presence of a ligand and/or find no binding partner on rabbit erythrocytes, in contrast to all other CGs (50). Except for C-GRIFIN, a lens-specific protein (48,49), these canonical (lactose-binding) members of the family have rather broad but individually distinct expression profiles, for example in cartilage and retina (60,61). To answer the question on the characteristics of expression of C-GRP systematic comparative analysis was performed.…”