Galectin

About: Galectin is a research topic. Over the lifetime, 2076 publications have been published within this topic receiving 103409 citations. The topic is also known as: IPR001079 & Galectin.

Intracellular galectins: Platforms for assembly of macromolecular complexes

Abstract: Although members of the galectin family were initially isolated on the basis of their saccharide-binding activity and cell surface localization, at least 11 of the 15 galectins identified in mammalian systems have been reported to be in the nucleus, as well as in the cytoplasm of cells. More interestingly, the precise intracellular localization and activity of the various galectins also cover a wide range. In most instances, distinct galectins give rise to the same or similar cellular responses. At the inner surface of plasma membranes, for example, galectin-1 (Gal1) and galectin-3 (Gal3) exhibit similar activities by binding to the Ras oncogene product to direct effector usage and signaling pathway. Gal1 and Gal3 also interact with Gemin4 and TFII-I as a part of ribonucleoprotein complexes and the two galectins have been documented to be required, but redundant, factors in pre-mRNA splicing. On the other hand, however, it appears that, although Gal3 and galectin-7 (Gal7) both bind to the apoptosis repressor protein Bcl-2, the ultimate cellular response is opposite: Gal3 is anti-apoptotic while Gal7 is pro-apoptotic. In all of these interactions, the ligands bind to the galectins through protein-protein interactions rather than via protein-carbohydrate recognition. The emergent general theme

Vertebrate galectins: endogenous regulators of ionotropic glutamate receptors?

Abstract: Lectins are proteins that bind specific carbohydrate residues on glycoproteins and glycolipids. In many cases, such binding alters the functional properties of the targeted protein or lipid and triggers a change in cell physiology. First characterized in plants, lectins with diverse carbohydrate specificity have subsequently been identified in animals, where they serve a variety of different functions including both intracellular regulation of protein sorting and extracellular interactions with carbohydrate moieties on the cell surface and in the extracellular matrix (Dodd & Drickamer, 2001). Both plant and animal lectins typically exist as dimers or multimers with their biological action being dependent on, or enhanced by, the ability to form cross links between protein subunits. In the case of ionotropic glutamate receptors (iGluRs) early work with plant lectins demonstrated a potentiating action on agonist-evoked currents recorded in insect and vertebrate cells. Vertebrates express three distinct iGluR families, but only α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate (KA) subtypes exhibit strong direct modulation by lectins while N-methyl-d-aspartate (NMDA) receptors are relatively unaffected. Brief exposure to wheat germ agglutinin, concanavalin A (ConA) or isolectin B4, with specificity for N-acetylglucosamine, mannose and β-galactosides, respectively, increases the amplitude of steady-state currents evoked via KA and/or AMPA receptors (Mayer & Vyklicky, 1989; Huettner, 1990). Now, a study from Geoff Swanson's lab in this issue of The Journal of Physiology (Copits et al. 2014) investigates the ability of vertebrate galectins, including recombinant human galectin-1, and congerin I and II from the conger eel, to regulate native and recombinant AMPA and KA receptors. Galectins bind specifically to β-galactoside glycoconjugates and the three galectins studied by Copits et al. (2014) can each form a bivalent homodimer. In contrast to tetravalent ConA, which substantially increases currents mediated by most AMPA and KA receptor isoforms, galectin application produced a remarkable diversity of effects on recombinant iGluRs depending on the specific subunits that were expressed and on which galectin was applied. For example, congerin caused a substantial slowing of AMPA receptor desensitization with an increase in steady-state current in cells expressing homomeric GluA4 and some of the cells expressing GluA1 whereas human galectin-1 had a greater effect on GluA1 than GluA4. In addition, congerin, but not galectin-1, reduced peak current with little change in kinetics in cells that expressed homomeric GluA2 or the GluA1/GluA2 heteromeric combination. Similarly, both eel and human galectins elicited a significantly greater slowing of desensitization in homomeric GluK2 KA receptors than homomeric GluK1 or heteromeric GluK2/GluK5 combinations. Modulation persisted in heterologous cells that were co-transfected with AMPA or KA receptor subunits together with their auxiliary subunits stargazin or Neto2, respectively. Mechanistically, galectin modulation of GluK2 was reduced by drugs that interfere with oligosaccharide processing and prevented by point mutations that eliminate three essential glycosylation sites at the interface between the receptor's amino terminal and ligand binding domains (Everts et al. 1999). In addition, GluK2 modulation was enhanced by linkers that stabilized the recombinant galectin as an obligate dimer, which is consistent with the idea that iGluR modulation involves crosslinking subunits via their attached glycoconjugates. In future work, it would be interesting to determine whether galectin–3, which can assemble into a pentameric oligomer, might elicit even stronger modulation. When tested on neuronal AMPA receptors in cultures prepared from rat hippocampus, congerin failed to change the amplitude or time course of agonist-evoked or spontaneous excitatory synaptic currents, possibly owing to additional modifications of glycoconjugates in central neurons that render them resistant to galectins or, alternatively, prior occupation of the binding site by endogenous lectins produced in the cultures that occlude the binding of acutely applied exogenous galectin. On the other hand, both congerin and human galectin-1 slowed desensitization of KA receptor-mediated currents recorded in freshly dissociated mouse sensory neurons, cells that are known to express galectin-1 and -3 as well as β-galactoside glycoconjugates (Jessell et al. 1990). Thus, Swanson and colleagues (Copits et al. 2014) have established the potential for native receptors to be modulated by endogenous lectins, but much work remains to determine where and when such regulation actually occurs. Mice lacking galectin-1 are viable but exhibit changes in primary afferent morphology and sensitivity (McGraw et al. 2005) as well as resistance to death of central neurons subsequent to pilocarpine-induced seizures (Bischoff et al. 2012). Whether or not these phenotypes involve alteration in iGluR modulation remains to be determined, but the availability of both galectin–1 and galectin–3 knock-outs should aid in unravelling their potential role in regulating excitatory amino acid receptors.

Back2Basics: animal lectins: an insight into a highly versatile recognition protein

Abstract: The rapid advancement of molecular research has contributed to the discovery of 'Lectin', a carbohydrate-binding protein which specifically interacts with receptors on surface glycan moieties that regulate various critical cellular activities. The first animal lectin reported was 'the asialoglycoprotein receptor' in mammalian cells which helped analyze how animal lectins differ in glycoconjugate binding. Animal lectins are classified into several families, depending on their diverse cellular localization, and the binding specificities of their Carbohydrate-Recognition Domain (CRD) modules. Earlier characterization of animal lectins classified them into two structural families, the C-type (Ca2+-dependent binding) and S-type galectins (sulfhydryl-dependent binding) lectins. The C-type lectin includes the most significant animal lectins, such as endocytic receptors, mannose receptors, selectins, and collectins. The recent developments in research based on the complexity of the carbohydrate ligands, the metabolic processes they perform, their expression levels, and their reliance on divalent cations have identified more than 100 animal lectins and classified them into around 13 different families, such as Calnexin, F-lectin, Intelectin, Chitinase-like lectin, F-box lectin, etc. Understanding their structure and expression patterns have aided in defining their significant functions including cell adhesion, antimicrobial activity, innate immunity, disease diagnostic biomarkers, and drug delivery through specific carbohydrate-protein interactions. Such extensive potential roles of animal lectins made it equally important to plant lectins among researchers. Hence, the review focuses on providing an overview of animal lectins, their taxonomy, structural characteristics, and functions in diverse aspects interconnected to their specific carbohydrate and glycoconjugate binding.

Galectin-9 and PD-L1 antibody blockade combination therapy inhibits tumour progression in pancreatic cancer.

Abstract: Background: The study aimed to evaluate the effect of a galectin-9 and PD-L1 combined blockade in pancreatic ductal adenocarcinoma (PDAC). Methods: The expression of galectin-9 and PD-L1 was analyzed in PDAC. Furthermore, we explored the therapeutic effect of combined anti-galectin-9 and anti-PD-L1 therapy on pancreatic cancer in vivo. Results: Higher expression of galectin-9 and PD-L1 was observed in human PDAC compared with the normal pancreas. Furthermore, in a murine model of PDAC, combined anti-galectin-9 and anti-PD-L1 treatment was associated with a greater decrease in tumor growth compared with treatment with either antibody therapy alone. Conclusion: Anti-PD-L1 antibody treatment for PDAC patients may be enhanced by inhibiting galectin-9.