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Galectin-12, a member of the galectin family of animal lectins, is preferentially expressed in adipocytes. We recently reported that this galectin is localized on lipid droplets, specialized organelles for fat storage. Galectin-12 regulates lipid degradation (lipolysis) by modulating lipolytic protein kinase A (PKA) signaling. Mice deficient in galectin-12 exhibit enhanced adipocyte lipolysis, increased mitochondria respiration, reduced adiposity and ameliorated insulin resistance associated with weight gain. The results suggest that galectin-12 may be a useful target for treatment of obesity-related metabolic conditions, such as insulin resistance, metabolic syndrome, and type 2 diabetes. Most previously described galectins largely reside in the cytosol, although they can also be induced to become associated with membrane-containing structures. Along with an in-depth characterization of galectin-12, this mini-review comments on this first report of a galectin normally localized specifically in an organelle that performs an important intracellular function. Further studies will help shed light on how this protein regulates cellular homeostasis, especially energy homeostasis, and provide additional insight into the intracellular functions of galectins.

Galectin-12, a member of the galectin family of animal lectins, is preferentially expressed in adipocytes. We recently reported that this galectin is localized on lipid droplets, specialized organelles for fat storage. Galectin-12 regulates lipid degradation (lipolysis) by modulating lipolytic protein kinase A (PKA) signaling. Mice deficient in galectin-12 exhibit enhanced adipocyte lipolysis, increased mitochondria respiration, reduced adiposity and ameliorated insulin resistance associated with weight gain. The results suggest that galectin-12 may be a useful target for treatment of obesity-related metabolic conditions, such as insulin resistance, metabolic syndrome, and type 2 diabetes. Most previously described galectins largely reside in the cytosol, although they can also be induced to become associated with membrane-containing structures. Along with an in-depth characterization of galectin-12, this mini-review comments on this first report of a galectin normally localized specifically in an organelle that performs an important intracellular function. Further studies will help shed light on how this protein regulates cellular homeostasis, especially energy homeostasis, and provide additional insight into the intracellular functions of galectins.

CD6 is a lymphocyte glycoprotein receptor that physically associates with the antigen‐specific receptor complex at the center of the immunological synapse, where it interacts with its ligand CD166/ALCAM. The present work reports the carbohydrate‐dependent interaction of CD6 and CD166/ALCAM with Galectin‐1 and ‐3, two well‐known soluble mammalian lectins. Both galectins interfered with superantigen‐induced T cell proliferation and cell adhesion phenomena mediated by the CD6‐CD166/ALCAM pair, while CD6 expression protected cells from galectin‐induced apoptosis. The results suggest that interaction of Galectin‐1 and ‐3 with CD6 and CD166/ALCAM might modulate some relevant aspects of T cell physiology.Galectin‐1 and ‐3 are two new interacting proteins for CD6 and its ligand CD166/ALCAM. Galectin‐1 and ‐3 modulate T cell proliferation and adhesion involving CD6‐CD166/ALCAM. The intracellular region of CD6 has protective effects against galectin‐induced T cell apoptosis. The interaction of Galectin‐1 and ‐3 with CD6 has a modulatory effect on T cell physiology. [ABSTRACT FROM AUTHOR]

Abstract: Galectins are highly expressed in epithelial cells and immune cells. In skin, they can be detected in keratinocytes, melanocytes, dendritic cells, macrophages, and T cells. Galectins are present outside and inside the cells and thus may exhibit different functions through extracellular and intracellular actions. Galectins can be involved in the pathogenesis of inflammatory skin diseases by affecting growth, apoptosis, maturation, activation, and motility of keratinocytes and immune cells. Expression of galectins may change depending on the cellular status, such as proliferation and activation. For example, galectin-3 expression is upregulated in T cells but downregulated in dendritic cells when these cells are activated. Furthermore, their expression may also change under pathological conditions. Understanding the function of each galectin in keratinocytes and different immune cell types may reveal how galectins contribute to the pathogenesis of immune-mediated skin diseases. [Copyright &y& Elsevier]

Galectins, β-galactoside-binding animal lectins, are differentially expressed by various immune cells as well as a wide range of other cell types. Extracellularly, galectins are able to exhibit bivalent or multivalent interactions with cell-surface glycans on various immune cells and exert various effects. These include cytokine and mediator production, cell adhesion, apoptosis, and chemoattraction. In addition, they can form lattices with cell-surface glycoprotein receptors, resulting in modulation of receptor functions, including clustering and endocytosis. Intracellularly, galectins can participate in signaling pathways and modulate biologic responses. These include apoptosis, cell differentiation, and cell migration. Thus, a large body of literature indicates that galectins play important roles in the immune and inflammatory responses through regulating the homeostasis and functions of immune cells. The use of mice deficient in individual galectins has provided additional evidence for the contributions of these proteins to these responses. Current research indicates that galectins play important roles in the development of acute inflammation as well as chronic inflammation associated with allergies, autoimmune diseases, atherosclerosis, infectious processes, and cancer. Thus, recombinant proteins or specific galectin inhibitors may be used as therapeutic agents for inflammatory diseases. [ABSTRACT FROM AUTHOR]

Many galectin family members are detected primarily intracellularly in most of the systems studied, although certain members can be found both inside and outside of cells. Specific functions that are consistent with their intracellular localization have now been documented for some of the galectins. Galectin-1 and -3 have been identified as redundant pre-mRNA splicing factors. Galectin-3, -7, and -12 have been shown to regulate cell growth and apoptosis, being either anti-apoptotic or pro-apoptotic. Galectin-3 and -12 have been shown to regulate the cell cycle. In some cases, the mechanisms by which galectins exert their functions have been partially delineated in relation to known intracellular pathways associated with these processes. In addition, a number of intracellular proteins involved in these processes have been identified as the interacting ligands of certain galectins. This review summarizes the intracellular activities displayed by several galectins and discusses the possible underlying mechanisms. [Copyright &y& Elsevier]

Nuclear presence of galectins suggests a role of these endogenous lectins in the regulation of transcription, pre-mRNA splicing and transport processes. Therefore, detection and localization of nuclear binding sites for galectins by a new methodological step, has potential to further functional analysis. In the first step of our model study we monitored the nuclear expression of galectins-1 and -3 in cultured stromal cells of human bone marrow and human/porcine keratinocytes. To enable detection and localization of galectin-specific binding sites, we used purified galectins biotinylated without loss of activity as cytochemical tool. The degree of labeling of the probes was determined by adapting two-dimensional gel electrophoresis and calculating pI changes in response to stepwise chemical modification of basic and acidic side chains by the biotinylation reagents. Binding studies revealed positivity for galectin-1, whereas galectins-3, -5, and -7 were not reactive with nuclear sites under identical conditions in bone marrow stromal cells and keratinocytes prepared from hair follicle enriched for stem cells. Inhibition by lactose indicated an involvement of the carbohydrate recognition domain in nuclear binding of galectin-1. Colocalization of the galectin-1-dependent signal with the SC35 splicing factor and sensitivity toward RNase treatment argued in favor of galectin binding in nuclear speckles, albeit only for a small fraction of the cells. Epidermal cells positive for galectin-1-binding sites expressed ΔNp63 known as a potential marker of stem cells. Based on cytokeratin expression cells with nuclear binding of labeled galectin-1 were basal and not suprabasal cells. Regarding proliferation, no relationship to the expression of a proliferation marker, Ki-67, was observed. The nucleolar signal colocalized with fibrillarin and nucleophosmin/B23 as representatives of nucleolar proteins in both types of studied cells. In conclusion, the application of labeled galectins to localize accessible binding sites adds a new aspect to the functional analysis of these lectins in the nucleus. [Copyright &y& Elsevier]

Allergic inflammatory diseases are a global public health concern affecting millions of people. Although there are several potential hypotheses, details regarding their molecular mechanisms are still ambiguous. Recently, a group of β-galactoside-binding proteins, galectins, have been revealed as important factors in altering allergic chronic inflammatory diseases. In this review, we describe the molecular and cellular basis of how galectins modulate inflammatory reactions. We also provide an overview of clinical features related to galectins. Finally, we discuss the potential issues that might lead to misrepresentation of the exact biological functions of galectins. [ABSTRACT FROM AUTHOR]