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.

Biophysical Studies on Calcium and Carbohydrate Binding to Carbohydrate Recognition Domain of Gal/GalNAc Lectin from Entamoeba histolytica: Insights into Host Cell Adhesion

Abstract: Entamoeba histolytica, an enteric parasite expresses a Gal/GalNAc-specific lectin that contributes to its virulence by establishing adhesion to host cell. In this study, carbohydrate recognition domain of Hgl (EhCRD) was purified and biophysical studies were conducted to understand the thermodynamic basis of its binding to carbohydrate and Ca(++) Here, we show that carbohydrate recognition domain (CRD) of the lectin binds to calcium through DPN motif. To decipher the role of calcium in carbohydrate binding and host cell adhesion, biophysical and cell-based studies were carried out. We demonstrated that the presence of the cation neither change the affinity of the lectin for carbohydrates nor alters its conformation. Mutation of the calcium-binding motif in EhCRD resulted in complete loss of ability to bind calcium but retained its affinity for carbohydrates. Purified EhCRD significantly diminished adhesion of the amebic trophozoites to Chinese Hamster Ovary (CHO) cells as well as triggered red blood cell agglutination. The calcium-binding defective mutant abrogated amebic adhesion to CHO cells similar to the wild-type protein, but it failed to agglutinate RBCs suggesting a differential role of the cation in these two processes. This study provides the first molecular description of the role of calcium in Gal/GalNAc mediated host cell adhesion.

[Galectins: a novel family of proteins involved in the regulation of the immune response. Implications in immunopathological processes].

Abstract: Galectins have emerged as a new family of closely related carbohydrate-binding proteins, which exert their functions by virtue of their ability to decipher glycocodes on complex glycoconjugates. They have been implicated in different immunological processes, such as lymphocyte adhesion, cytokine production, cell growth regulation, apoptosis and central and peripheral immune tolerance. In the present article we analyze the implications of this protein family in different immune pathologies with up- or down-regulated immune responses, such as autoimmune disorders, acute and chronic inflammation, allergic diseases, infection and metastases. The use of recombinant galectins or their antagonists will have future implications in the diagnosis, prognosis and treatment of these diseases, widening the horizons of molecular immunopathology.

Galectin-9 induces atypical ubiquitination leading to cell death in PC-3 prostate cancer cells.

Abstract: Galectin-9 is the most potent inducer of cell death in lymphomas and other malignant cell types among the members of the galectin family. We investigated the mechanism of galectin-9-induced cell death in PC-3 prostate cancer cells in comparison with in Jurkat T cells. Galectin-9 induced apoptotic cell death in Jurkat cells, as typically revealed by DNA ladder formation. On the other hand, DNA ladder formation and other features of apoptosis were not apparent in PC-3 cells undergoing galectin-9-induced death. Exogenous galectin-9 was endocytosed and destined to the lysosomal compartment in PC-3 cells. The internalized galectin-9 was resistant to detergent solubilization but was solubilized with lactose. Agents inhibiting actin filament dynamics abolished the internalization and cytocidal effect of galectin-9 in PC-3 but not Jurkat cells. Galectin-9 induced accumulation of ubiquitinated proteins, possibly heterogeneously ubiquitinated and/or monoubiquitinated proteins, in PC-3 cells. PYR-41, an inhibitor of the ubiquitin-activating E1 enzyme, suppressed the cytocidal effect of galectin-9. Although ubiquitination was upregulated also in Jurkat cells by galectin-9, PYR-41 was ineffective against galectin-9-induced cell death. Colocalization of ubiquitinated proteins and LAMP-1 was detectable in PC-3 cells treated with galectin-9. The ubiquitinated proteins were recovered in the insoluble fraction upon cell fractionation. In contrast, ubiquitinated proteins that accumulated after treatment with proteasome inhibitors did not co-localize with LAMP-1 and were mainly recovered in soluble fraction. The results suggest that atypical ubiquitination and accumulation of ubiquitinated proteins in lysosomes play a pivotal role in galectin-9-induced non-apoptotic death in PC-3 cells.

KSHV downregulation of galectin-3 in Kaposi’s sarcoma

Abstract: Galectins are a family of proteins that share an affinity for beta-galactoside containing glycoconjugates. In prostate, ovarian and breast cancer, downregulation of galectin-3 is associated with malignancy and tumor progression. Kaposi's sarcoma (KS) is characterized as an angioproliferative tumor of vascular endothelial cells and produces rare B cell lymphoproliferative diseases in the form of primary effusion lymphomas and some forms of multicentric Castleman's disease. Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of KS. We found reduced levels of galectin-3 expression in a significant fraction of latency-associated nuclear antigen (LANA)-positive spindle cell regions in human archival KS tissue and as measured in KS tissue microarrays. Here we demonstrate that galectin-3 protein expression is downregulated 10-fold in 10-day KSHV-infected dermal microvascular endothelial cells (DMVEC) accompanied by downregulation of message. There is loss of galectin-3 staining in KSHV-infected DMVEC by dual labeled immunohistochemistry in LANA-positive spindle cells. We observed a consistent downregulation of galectin-3 by time-course transcriptional analysis. Of the galectins assayed, only galectin-1 was also downregulated in KSHV-infected DMVEC. We examined 86 KS tumors; 19 were LANA positive (22%) and 67 LANA negative (78%). All 86 tumors were found to be galectin-3 positive; 11 of 19 showed reduced expression of galectin-3 in LANA-positive spindle cell regions. Our data suggest that KSHV vFLIP and LANA are the viral genes targeting galectin-3 downregulation. The contribution of host factors to the pathogenesis of KS is essential for early detection and development of innovative therapies for treatment.