Galectin-8 binds specific β1 integrins and induces polarized spreading highlighted by asymmetric lamellipodia in Jurkat T cells

Cárcamo, Claudia; Pardo, Evelyn; Oyanadel, Claudia; Bravo‐Zehnder, Marcela; Bull, Paulina; Cáceres, Mónica; Martı́nez, Jorge; Massardo, Loreto; Jacobelli, S; González, Alfonso; Soza, Andrea

doi:10.1016/j.yexcr.2005.10.025

Cited by 76 publications

(90 citation statements)

References 72 publications

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“…For example N-glycans on the 4-subunit are once mentioned as main binding partner while other authors do not report binding to this subunit. Similar discrepancies were noticed for other subunits (Cárcamo et al, 2006;Diskin et al, 2009;Hadari et al, 2000;Nishi et al, 2003;Yamamoto et al, 2008). This might be explained by tissue-or cell-specific glycosylation patterns of the single subunits.…”

Section: Cell-surface Glycoproteins As Binding Partners Of Galectinssupporting

confidence: 57%

Galectins: Structures, Binding Properties and Function in Cell Adhesion

Römer¹,

Elling²

2011

Biomaterials - Physics and Chemistry

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Section: Cell-surface Glycoproteins As Binding Partners Of Galectinssupporting

confidence: 57%

Galectins: Structures, Binding Properties and Function in Cell Adhesion

Römer¹,

Elling²

2011

Biomaterials - Physics and Chemistry

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“…However, these studies did not provide evidence of functional implications for this putative interaction. Tribulatti et al, (2009) studied Gal-8 bound proteins by mass spectrometry analysis in mice splenocytes and found several leukocyte surface glycoproteins, including previously reported integrins (Hadari et al, 2000;Zick et al, 2004;Cárcamo et al, 2006;Yamamoto et al, 2008) and CD45, as candidate counter-receptors. Their functional studies then focused on CD45, leaving LFA-1 unexplored (Tribulatti et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Galectin-8 binds to LFA-1, blocks its interaction with ICAM-1 and is counteracted by anti-Gal-8 autoantibodies isolated from lupus patients

et al. 2013

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Galectin-8 belongs to a family of mammalian lectins that recognize glycoconjugates present on diff erent cell surface components and modulate a variety of cellular processes. A role of Gal-8 in the immune system has been proposed based on its eff ects in immune cells, including T and B lymphocytes, as well as the presence of anti-Gal-8 autoantibodies in the prototypic autoimmune disease systemic lupus erythematosus (SLE). We have previously described that Gal-8 induces apoptosis in activated T cells interacting with certain β1 integrins and this eff ect is counteracted by the anti-Gal-8 autoantibodies. Given that Gal-8 can potentially interact with several glycoproteins, here we analyzed the β2 integrin Lymphocyte Function-Associated Antigen-1 (LFA-1), which is involved in leukocyte cell adhesion and immunological synapses. We show by GST-pull down assays that Gal-8 interacts with LFA-1 and this interaction is inhibited by anti-Gal-8 autoantibodies isolated from SLE patients. In cell adhesion assays, Gal-8 precluded the interaction of LFA-1 with its ligand Intracellular Adhesion Molecule-1 (ICAM-1). These results suggest that Gal-8 can exert immunosuppressive action not only by inducing apoptosis in activated T cells but also by negatively modulating the crucial function of LFA-1 in the immune system, while function-blocking autoantibodies counteract these eff ects.

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“…Tissue culture plastics were purchased from Nalgene Nunc (Thermo Fisher). Recombinant human GST-Gal-8 and Gal-8 released by thrombin cut from this chimera protein were prepared as previously described (10). Wild type PLD-2 and its dominant negative version were kindly provided by Dr. Michael Frohman (Stony Brook University).…”

Section: Methodsmentioning

confidence: 99%

“…4 is one of the most widely expressed galectins in human tissues (21,22) and cancerous cells (23,24). Depending on the cell context and mode of presentation, either as soluble stimulus or extracellular matrix, Gal-8 can promote cell adhesion, spreading, growth, and apoptosis (6,7,9,10,22,25). Its role has been mostly studied in relation to tumor malignancy (23,24).…”

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confidence: 99%

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Galectin-8 Induces Apoptosis in Jurkat T Cells by Phosphatidic Acid-mediated ERK1/2 Activation Supported by Protein Kinase A Down-regulation

Norambuena

Metz

Vicuña

et al. 2009

Journal of Biological Chemistry

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Galectins have been implicated in T cell homeostasis playing complementary pro-apoptotic roles. Here we show that galectin-8 (Gal-8) is a potent pro-apoptotic agent in Jurkat T cells inducing a complex phospholipase D/phosphatidic acid signaling pathway that has not been reported for any galectin before. Gal-8 increases phosphatidic signaling, which enhances the activity of both ERK1/2 and type 4 phosphodiesterases (PDE4), with a subsequent decrease in basal protein kinase A activity. Strikingly, rolipram inhibition of PDE4 decreases ERK1/2 activity. Thus Gal-8-induced PDE4 activation releases a negative influence of cAMP/protein kinase A on ERK1/2. The resulting strong ERK1/2 activation leads to expression of the death factor Fas ligand and caspase-mediated apoptosis. Several conditions that decrease ERK1/2 activity also decrease apoptosis, such as anti-Fas ligand blocking antibodies. In addition, experiments with freshly isolated human peripheral blood mononuclear cells, previously stimulated with anti-CD3 and anti-CD28, show that Gal-8 is pro-apoptotic on activated T cells, most likely on a subpopulation of them. Anti-Gal-8 autoantibodies from patients with systemic lupus erythematosus block the apoptotic effect of Gal-8. These results implicate Gal-8 as a novel T cell suppressive factor, which can be counterbalanced by functionblocking autoantibodies in autoimmunity.

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Galectin-8 binds specific β1 integrins and induces polarized spreading highlighted by asymmetric lamellipodia in Jurkat T cells

Cited by 76 publications

References 72 publications

Galectins: Structures, Binding Properties and Function in Cell Adhesion

Galectins: Structures, Binding Properties and Function in Cell Adhesion

Galectin-8 binds to LFA-1, blocks its interaction with ICAM-1 and is counteracted by anti-Gal-8 autoantibodies isolated from lupus patients

Galectin-8 Induces Apoptosis in Jurkat T Cells by Phosphatidic Acid-mediated ERK1/2 Activation Supported by Protein Kinase A Down-regulation

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