scispace - formally typeset
Search or ask a question
Topic

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.


Papers
More filters
Journal ArticleDOI
TL;DR: Results from cross-linking studies in transgenic mouse lenses designed for overexpression of His-tagged human alphaA-crystallin support the hypothesis that GRIFIN is a novel binding partner of alpha- Crystallin in the lens.
Abstract: The mammalian lens contains a very high concentration of soluble protein, estimated to be approximately 350 mg/mL, to provide refractive power. The majority of lens proteins belong to one of three major groups, which are designated α-, β-, and γ-crystallins (1). The α-crystallins, which constitute ~30% of lens protein, are heteromeric oligomers composed of two gene products, αA and αB, present in a 3:1 molar ratio in human lenses. The two ~20 kDa gene products assemble into oligomers with an average size of 600 kDa, indicating each complex contains approximately 30 monomers (2). The quaternary structure of α-crystallin is very dynamic due to the ability of αA- and αB-crystallin subunits to exchange between complexes in a temperature and time-dependent manner (3, 4). Like other members of the small heat shock protein (sHSP)1 family, α-crystallin has a chaperone-like activity defined by the ability to bind denatured or unstable proteins and prevent their aggregation. While sHSPs have minimal, if any, capacity to actively refold proteins, current evidence from in vitro studies suggests that they can transfer captured protein substrates to conventional chaperones for ATP-dependent refolding (5, 6). Mice with targeted disruption of the αA gene develop early cataracts caused by accumulation of light scattering protein aggregates (7), consistent with the view that a critical role for α-crystallin in the lens is maintenance of transparency. However, the mechanisms by which α-crystallin recognizes unstable and/or unfolded proteins are still unknown. Recent studies demonstrate that α-crystallin can interact with a wide variety of proteins involved with signaling and cytoskeletal structure (8). α-Crystallin interacts with various components of the cytoskeleton, including actin, vimentin, CP49, and filensin, but the effect this confers is variable (9–12). α-Crystallin stabilizes actin filaments both in vivo and in vitro when subjected to stresses, including heat and cytochalasin D (11, 12). However, the interaction with type III intermediate filament monomers prevents their assembly (10). α-Crystallin also associates with plasma membranes from lens fiber cells, and the total amount bound increases with age, diabetes, and cataract (13, 14). In vitro analysis of this binding suggests the interaction is hydrophobic and not dependent on a specific type of lipid (15). Beyond these insoluble cellular structures, the soluble protein interactions of α-crystallin are largely unknown. In vitro data suggest that intermolecular interactions occur between α-crystallin and a variety of signaling proteins and metabolic enzymes under native conditions (8, 16); however, the physiological importance is difficult to gauge since most of the identified proteins are expressed in the lens in small amounts, if at all (8). Judging from in vitro studies, substrate binding is significantly enhanced by ATP (16), although little is known about the effect this may have on its ability to bind and/or refold captured proteins (16–18). The goal of our study is to identify proteins that interact with α-crystallin in the context of the intact lens. As in previous studies which used epitope tagging to selectively enrich proteins that interact with HSP16.6 in the cyanobacterium Synechocystis sp. PCC 6803 (19), we have utilized a transgenic mouse model designed for lens-specific expression of His-tagged human αA-crystallin (20). Protein–protein interactions in the intact lens were fixed by a brief treatment with a cross-linking agent. α-Crystallin complexes that contain the bait transgene product were isolated by immobilized metal affinity chromatography (IMAC) for analysis by liquid chromatography–tandem mass spectrometry (LC–MS/MS). As expected, the majority of interacting proteins captured by this approach were crystallins. Proteomic analysis of crystallin complexes isolated from transgenic lenses identified peptides derived from galectin-related interfiber protein (GRIFIN). Binding of GRIFIN by α-crystallin was confirmed using a filter-based binding assay. Dissociation constants and effects of ATP on binding are consistent with physiologically relevant interactions between α-crystallin and GRIFIN.

25 citations

Journal ArticleDOI
TL;DR: This review aims to analyze the complexity and importance of glycoconjugates and their molecular interaction network in the hypoxic context of many solid tumors.
Abstract: Post-translational and co-translational enzymatic addition of glycans (glycosylation) to proteins, lipids, and other carbohydrates, is a powerful regulator of the molecular machinery involved in cell cycle, adhesion, invasion, and signal transduction, and is usually seen in both in vivo and in vitro cancer models. Glycosyltransferases can alter the glycosylation pattern of normal cells, subsequently leading to the establishment and progression of several diseases, including cancer. Furthermore, a growing amount of research has shown that different oxygen tensions, mainly hypoxia, leads to a markedly altered glycosylation, resulting in altered glycan-receptor interactions. Alteration of intracellular glucose metabolism, from aerobic cellular respiration to anaerobic glycolysis, inhibition of integrin 3α1β translocation to the plasma membrane, decreased 1,2-fucosylation of cell-surface glycans, and galectin overexpression are some consequences of the hypoxic tumor microenvironment. Additionally, increased expression of gangliosides carrying N-glycolyl sialic acid can also be significantly affected by hypoxia. For all these reasons, it is possible to realize that hypoxia strongly alters glycobiologic events within tumors, leading to changes in their behavior. This review aims to analyze the complexity and importance of glycoconjugates and their molecular interaction network in the hypoxic context of many solid tumors.

25 citations

Journal ArticleDOI
TL;DR: The results suggest that the upregulated Lamp-1 expression at confluence could be involved in keratinocyte differentiation, but apparently not through interaction with galectin-3.
Abstract: Lysosomes and their components are suspected to be involved in epidermal differentiation. In this study, lysosomal enzyme activities, expression of the lysosome-associated membrane protein 1 (Lamp-1) and expression of the epidermal galectins-1, -3 and -7 were investigated in human keratinocytes cultured at different cell densities (subconfluence, confluence and postconfluence) in order to induce differentiation. Detected by Western blot and immunofluorescence, Lamp-1 expression is transiently upregulated at culture confluence, but reduced at postconfluence. Northern blot analyses performed on subconfluent, confluent and post-confluent cultures of keratinocytes show that Lamp-1 mRNA expression is also upregulated at culture confluence, but downregulated at postconfluence. Measurements of lysosomal enzyme activities indicate a transient upregulation at culture confluence, whereas cathepsins B, C and L are particularly downregulated at postconfluence. Cell density and differentiation of epidermal cells also differentially regulates galectin expression in autocrine cultures. As the expression of galectin-1 mRNA is high in subconfluent cells, it is assumed to be associated with their proliferative state. On the other hand, as the mRNA levels for galectins-3 and -7 are notably upregulated at culture confluence (galectin-7) or at postconfluence (galectin-3), their expression is thought to be related to the differentiated state of keratinocytes. However, we collected evidence by confocal microscopy that galectin-3 and Lamp-1 do not colocalize in vitro in keratinocytes. Altogether, our results suggest that the upregulated Lamp-1 expression at confluence could be involved in keratinocyte differentiation, but apparently not through interaction with galectin-3.

25 citations

Journal ArticleDOI
TL;DR: The authors showed that perturbation of global cellular patterns of protein glycosylation by modulation of metabolic flux affects clathrin-independent endocytosis and cargo-specific effects.

25 citations

Journal ArticleDOI
30 Jun 2015-PLOS ONE
TL;DR: Treatment with Galectin-8 (Gal-8), a tandem-repeat member of the galectin family, reduces retinal pathology and prevents photoreceptor cell damage in a murine model of experimental autoimmune uveitis and emerges as an attractive therapeutic candidate not only for treating retinal autoimmune diseases, but also for other TH1- and TH17-mediated inflammatory disorders.
Abstract: Galectins have emerged as potent immunoregulatory agents that control chronic inflammation through distinct mechanisms. Here, we report that treatment with Galectin-8 (Gal-8), a tandem-repeat member of the galectin family, reduces retinal pathology and prevents photoreceptor cell damage in a murine model of experimental autoimmune uveitis. Gal-8 treatment increased the number of regulatory T cells (Treg) in both the draining lymph node (dLN) and the inflamed retina. Moreover, a greater percentage of Treg cells in the dLN and retina of Gal-8 treated animals expressed the inhibitory coreceptor cytotoxic T lymphocyte antigen (CTLA)-4, the immunosuppressive cytokine IL-10, and the tissue-homing integrin CD103. Treg cells in the retina of Gal-8-treated mice were primarily inducible Treg cells that lack the expression of neuropilin-1. In addition, Gal-8 treatment blunted production of inflammatory cytokines by retinal T helper type (TH) 1 and TH17 cells. The effect of Gal-8 on T cell differentiation and/or function was specific for tissues undergoing an active immune response, as Gal-8 treatment had no effect on T cell populations in the spleen. Given the need for rational therapies for managing human uveitis, Gal-8 emerges as an attractive therapeutic candidate not only for treating retinal autoimmune diseases, but also for other TH1- and TH17-mediated inflammatory disorders.

25 citations


Network Information
Related Topics (5)
Cell culture
133.3K papers, 5.3M citations
85% related
Signal transduction
122.6K papers, 8.2M citations
84% related
Immune system
182.8K papers, 7.9M citations
83% related
Receptor
159.3K papers, 8.2M citations
82% related
Cellular differentiation
90.9K papers, 6M citations
82% related
Performance
Metrics
No. of papers in the topic in previous years
YearPapers
2023182
2022176
2021107
2020120
201995
2018119