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.

Interaction profile of galectin-5 with free saccharides and mammalian glycoproteins: probing its fine specificity and the effect of naturally clustered ligand presentation.

Abstract: Cell-surface glycans are functional docking sites for tissue lectins such as the members of the galectin family. This interaction triggers a wide variety of responses; hence, there is a keen interest in defining its structural features. Toward this aim, we have used enzyme-linked lectinosorbent (ELLSA) and inhibition assays with the prototype rat galectin-5 and panels of free saccharides and glycoconjugates. Among 45 natural glycans tested for lectin binding, galectin-5 reacted best with glycoproteins (gps) presenting a high density of Galbeta1-3/4GlcNAc (I/II) and multiantennary N-glycans with II termini. Their reactivities, on a nanogram basis, were up to 4.3 x 10(2), 3.2 x 10(2), 2.5 x 10(2), and 1.7 x 10(4) times higher than monomeric Galbeta1-3/4GlcNAc (I/II), triantennary-II (Tri-II), and Gal, respectively. Galectin-5 also bound well to several blood group type B (Galalpha1-3Gal)- and A (GalNAcalpha1-3Gal)-containing gps. It reacted weakly or not at all with tumor-associated Tn (GalNAcalpha1-Ser/Thr) and sialylated gps. Among the mono-, di-, and oligosaccharides and mammalian glycoconjugates tested, blood group B-active II (Galalpha1-3Gal beta1-4GlcNAc), B-active IIbeta1-3L (Galalpha1-3Galbeta1-4GlcNAc beta1-3Galbeta1-4Glc), and Tri-II were the best. It is concluded that (1) Galbeta1-3/4GlcNAc and other Galbeta1-related oligosaccharides with alpha1-3 extensions are essential for binding, their polyvalent form in cellular glycoconjugates being a key recognition force for galectin-5; (2) the combining site of galectin-5 appears to be of a shallow-groove type sufficiently large to accommodate a substituted beta-galactoside, especially with alpha-anomeric extension at the non-reducing end (e.g., human blood group B-active II and B-active IIbeta1-3L); (3) the preference within beta-anomeric positioning is Galbeta1-4 > or = Galbeta1-3 > Galbeta1-6; and (4) hydrophobic interactions in the vicinity of the core galactose unit can enhance binding. These results are important for the systematic comparison of ligand selection in this family of adhesion/growth-regulatory effectors with potential for medical applications.

Galectin-3: its role in asthma and potential as an anti-inflammatory target

Abstract: Galectins constitute an evolutionary conserved family that bind to β-galactosides. Increasing evidence shows that galectins are involved in many fundamental biological processes such as cellular communication, inflammation, differentiation and apoptosis. Changes in galectin-3 (Gal-3) expression are commonly seen in cancer and pre-cancerous conditions, and Gal-3 may be involved in the regulation of diverse cancer cell activities that contribute to tumourigenesis, cancer progression and metastasis. In addition, Gal-3 is a pro-inflammatory regulator in rheumatoid arthritis. Gal-3 has been shown to be involved in many aspects in allergic inflammation, such as eosinophil recruitment, airway remodeling, development of a Th2 phenotype as well as increased expression of inflammatory mediators. In an in vivo model it was shown that bronchoalveolar lavage (BAL) fluid from ovalbumin-challenged mice contained significantly higher levels of Gal-3 compared to control mice. The molecular mechanisms of Gal-3 in human asthma have not been fully elucidated. This review will focus on what is known about the Gal-3 and its role in the pathophysiological mechanisms of asthma to evaluate the potential of Gal-3 as a biomarker and therapeutic target of asthma.

Novel Interaction of MUC4 and Galectin: Potential Pathobiological Implications for Metastasis in Lethal Pancreatic Cancer

Abstract: Purpose Several studies have reported aberrant expression of MUC4 in pancreatic cancer (PC), which is associated with tumorigenicity and metastasis. Mechanisms through which MUC4 promote metastasis of PC cells to distant organs are poorly defined. Experimental design Identification of MUC4-galectin-3 interaction and its effect on the adhesion of cancer cells to endothelial cells were done by immunoprecipitation and cell-cell adhesion assays, respectively. Serum galectin-3 level for normal and PC patients were evaluated through ELISA. Results In the present study, we have provided clinical evidence that the level of galectin-3 is significantly elevated in the sera of PC patients with metastatic disease compared with patients without metastasis (P = 0.04) and healthy controls (P = 0.00001). Importantly, for the first time, we demonstrate that MUC4 present on the surface of circulating PC cells plays a significant role in the transient and reversible attachment (docking) of circulating tumor cells to the surface of endothelial cells. Further, exogenous galectin-3 at concentrations similar to that found in the sera of PC patients interacts with MUC4 via surface glycans such as T antigens, which results in the clustering of MUC4 on the cell surface and a stronger attachment (locking) of circulating tumor cells to the endothelium. Conclusions Altogether, these findings suggest that PC cell-associated MUC4 helps in the docking of tumor cells on the endothelial surface. During cancer progression, MUC4-galectin-3 interaction-mediated clustering of MUC4 may expose the surface adhesion molecules, which in turn promotes a stronger attachment (locking) of tumor cells to the endothelial surface.

The molecular basis for the evolution of the metazoan bodyplan : extracellular matrix-mediated morphogenesis in marine demosponges

Abstract: Molecular data on development/differentiation and on comparative genomics allow insights into the genetic basis of the evolution of a bodyplan. Sponges (phylum Porifera) are animals that are the (still extant) stem group with the hypothetical Urmetazoa as the earliest common ancestor of all metazoans; they possess the basic features of the characteristic metazoan bodyplan also valid for the animals of the crown taxa. Here we describe three homeobox genes from the demosponge Suberites domuncula whose deduced proteins (HOXa1_SUBDO, HOXb1_SUBDO, HOXc1_SUBDO) are to be grouped with the Antennapedia class of homeoproteins (subclasses TIx-Hox11 and NK-2). In addition, a cDNA encoding a LIM/homeobox protein has been isolated which comprises high sequence similarity to the related LIM homeodomain (HD) proteins in its LIM as well as in its HD domains. To elucidate the potential function of these proteins in the sponge a new in vitro system was developed. Primmorphs which are formed from dissociated cells were grown on a homologous galectin matrix. This galectin cDNA was cloned and the recombinant protein was used for the preparation of the matrix. The galectin/polylysine matrix induced in primmorphs the formation of channels, one major morphogenetic process in sponges. Under such conditions the expression of the gene encoding the LIM/homeobox protein is strongly upregulated, while the expression of the other homeobox genes remains unchanged or is even downregulated. Competition experiments with galactosylceramides isolated from S. domuncula were performed. They revealed that a β-galactosylceramide, named Sdgal-1, prevented the expression of the LIM gene on the galectin matrix, while Sdgal-2, a diglycosylceramide having a terminal α-glycosidically linked galactose, caused no effect on the formation of channels in primmorphs or on LIM expression. This study demonstrates for the first time that an extracellular matrix molecule, galectin, induces a morphogenetic process in sponges which is very likely caused by a LIM/homeobox protein. Furthermore, a new model is introduced (galectin-caused channel formation in sponge primmorphs) to investigate basic pathways, thus allowing new insights into the functional molecular evolution of Metazoa.